Glial grafting for demyelinating disease
Abstract
Remyelination of demyelinated central nervous system (CNS) axons is considered as a potential treatment for multiple sclerosis, and it has been achieved in experimental models of demyelination by transplantation of pro-myelinating cells. However, the experiments undertaken have not addressed the need for tissue-type matching in order to achieve graft-mediated remyelination since they were performed in conditions in which the chance for graft rejection was minimized. This article focuses on the factors determining survival of allogeneic oligodendrocyte lineage cells and their contribution to the remyelination of demyelinating CNS lesions. The immune status of the CNS as well as the suitability of different models of demyelination for graft rejection studies are discussed, and ways of enhancing allogeneic oligodendrocyte-mediated remyelination are presented. Finally, the effects of glial graft rejection on host remyelination are described, highlighting the potential benefits of the acute CNS inflammatory response for myelin repair.
References
Abina M.A, Lee M.G, Descamps V, Cordier L, Lopez M, Perricaudet M& Haddada H . 1996LacZ gene transfer into tumor cells abrogates tumorigenicity and protects mice against the development of further tumors. Gene Ther. 3, 212–216. PubMed, ISI, Google ScholarAchim C.L& Wiley C.A . 1992Expression of major histocompatibility complex antigens in the brains of patients with progressive multifocal leukoencephalopathy. J. Neuropathol. Exp. Neurol. 51, 257–263. Crossref, PubMed, ISI, Google ScholarAder M, Schachner M& Bartsch U . 2001Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin-associated glycoprotein and Fyn tyrosine kinase. Eur. J. Neurosci. 14, 561–566.doi:10.1046/j.0953-816x.2001.01673.x. . Crossref, PubMed, ISI, Google ScholarAloisi F, Ria F, Columba-Cabezas S, Hess H, Penna G& Adorini L . 1999Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation. Eur. J. Immunol. 29, 2705–2714.doi:10.1002/(SICI)1521-4141(199909)29:09<2705::AID-IMMU2705>3.3.CO;2-T. . Crossref, PubMed, ISI, Google ScholarAloisi F, Ria F& Adorini L . 2000Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol. Today. 21, 141–147.doi:10.1016/S0167-5699(99)01512-1. . Crossref, PubMed, Google ScholarAndersson G, Illigens B.M, Johnson K.W, Calderhead D, LeGuern C, Benichou G, White-Scharf M.E& Down J.D . 2003Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice. Blood. 101, 4305–4312.doi:10.1182/blood-2002-06-1649. . Crossref, PubMed, ISI, Google ScholarBailey K.A, Drago J& Bartlett P.F . 1994Neuronal progenitors identified by their inability to express class I histocompatibility antigens in response to interferon-gamma. J. Neurosci. Res. 39, 166–177.doi:10.1002/jnr.490390207. . Crossref, PubMed, ISI, Google ScholarBarker C.F& Billingham R.E . 1977Immunologically privileged sites. Adv. Immunol. 25, 1–54. PubMed, ISI, Google ScholarBaron-Van Evercooren A& Blakemore W.F Remyelination through engraftment. Myelin biology and disorders& Lazzarini R.A vol. 12004pp. 143–172. Eds. New York:Elsevier. Google ScholarBartlett P.F, Rosenfeld J, Bailey K.A, Cheesman H, Harvey A.R& Kerr R.S . 1990Allograft rejection overcome by immunoselection of neuronal precursor cells. Prog. Brain Res. 82, 153–160. Crossref, PubMed, ISI, Google ScholarBauer J, Bradl M, Hickey W.F, Forss-Petter S, Breitschopf H, Linington C, Wekerle H& Lassmann H . 1998T cell apoptosis in inflammatory brain lesions: destruction of T cells does not depend on antigen recognition. Am. J. Pathol. 153, 715–724. Crossref, PubMed, ISI, Google ScholarBellinger D.L, Felten S.Y, Lorton D& Felten D.L Innervation of lymphoid organs and neurotransmitter–lymphocyte interactions. Immunology of the nervous system, Keane R.W& Hickey W.F . 1997pp. 226–329. Eds. Oxford:Oxford University Press. Google ScholarBenveniste E.N . 1992Inflammatory cytokines within the central nervous system: sources, function, and mechanism of action. Am. J. Physiol. 263, C1–C16. Crossref, PubMed, ISI, Google ScholarBerger T, Weerth S, Kojima K, Linington C, Wekerle H& Lassmann H . 1997Experimental autoimmune encephalomyelitis: the antigen specificity of T lymphocytes determines the topography of lesions in the central and peripheral nervous system. Lab. Invest. 76, 355–364. PubMed, ISI, Google ScholarBergsteindottir K, Brennan A, Jessen K.R& Mirsky R . 1992In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules. Proc. Natl Acad. Sci. USA. 89, 9054–9058. Crossref, PubMed, ISI, Google ScholarBieber A.J, Kerr S& Rodriguez M . 2003Efficient central nervous system remyelination requires T cells. Ann. Neurol. 53, 680–684.doi:10.1002/ana.10578. . Crossref, PubMed, ISI, Google ScholarBiffiger K, Bartsch S, Montag D, Aguzzi A, Schachner M& Bartsch U . 2000Severe hypomyelination of the murine CNS in the absence of myelin-associated glycoprotein and fyn tyrosine kinase. J. Neurosci. 20, 7430–7437. Crossref, PubMed, ISI, Google ScholarBlakemore W.F& Patterson R.C . 1978Suppression of remyelination in the CNS by X-irradiation. Acta Neuropathol. (Berl.). 42, 105–113.doi:10.1007/BF00690975. . Crossref, PubMed, ISI, Google ScholarBlakemore W.F, Crang A.J, Franklin R.J, Tang K& Ryder S . 1995Glial cell transplants that are subsequently rejected can be used to influence regeneration of glial cell environments in the CNS. Glia. 13, 79–91.doi:10.1002/glia.440130202. . Crossref, PubMed, ISI, Google ScholarBlakemore W.F, Chari D.M, Gilson J.M& Crang A.J . 2002Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS. Glia. 38, 155–168.doi:10.1002/glia.10067. . Crossref, PubMed, ISI, Google ScholarBoison D& Stoffel W . 1989Myelin-deficient rat: a point mutation in exon III (A–C, Thr75–Pro) of the myelin proteolipid protein causes dysmyelination and oligodendrocyte death. EMBO J. 8, 3295–3302. Crossref, PubMed, ISI, Google ScholarBrabb T, von Dassow P, Ordonez N, Schnabel B, Duke B& Goverman J . 2000In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity. J. Exp. Med. 192, 871–880.doi:10.1084/jem.192.6.871. . Crossref, PubMed, ISI, Google ScholarBradbury M.W& Westrop R.J . 1983Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit. J. Physiol. 339, 519–534. Crossref, PubMed, ISI, Google ScholarBroadwell R.D, Baker B.J, Ebert P.S& Hickey W.F . 1994Allografts of CNS tissue possess a blood–brain barrier. III. Neuropathological, methodological, and immunological considerations. Microsc. Res. Tech. 27, 471–494.doi:10.1002/jemt.1070270603. . Crossref, PubMed, ISI, Google ScholarButtini M, Limonta S& Boddeke H.W . 1996Peripheral administration of lipopolysaccharide induces activation of microglial cells in rat brain. Neurochem. Int. 29, 25–35.doi:10.1016/0197-0186(95)00141-7. . Crossref, PubMed, ISI, Google ScholarBuzanska L, Machaj E.K, Zablocka B, Pojda Z& Domanska-Janik K . 2002Human cord blood-derived cells attain neuronal and glial features in vitro. J. Cell Sci. 115, 2131–2138. Crossref, PubMed, ISI, Google ScholarCaversaccio M, Peschel O& Arnold W . 1996The drainage of cerebrospinal fluid into the lymphatic system of the neck in humans. ORL J. Otorhinolaryngol. Relat. Spec. 58, 164–166. Crossref, PubMed, ISI, Google ScholarChang A, Nishiyama A, Peterson J, Prineas J& Trapp B.D . 2000NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J. Neurosci. 20, 6404–6412. Crossref, PubMed, ISI, Google ScholarChang A, Tourtellotte W.W, Rudick R& Trapp B.D . 2002Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N. Engl. J. Med. 346, 165–173.doi:10.1056/NEJMoa010994. . Crossref, PubMed, ISI, Google ScholarChari D.M& Blakemore W.F . 2002New insights into remyelination failure in multiple sclerosis: implications for glial cell transplantation. Mult. Scler. 8, 271–277.doi:10.1191/1352458502ms842oa. . Crossref, PubMed, ISI, Google ScholarChari D.M, Crang A.J& Blakemore W.F . 2003Decline in rate of colonization of oligodendrocyte progenitor cell (OPC)-depleted tissue by adult OPCs with age. J. Neuropathol. Exp. Neurol. 62, 908–916. Crossref, PubMed, ISI, Google ScholarCornet A, Savidge T.C, Cabarrocas J, Deng W.L, Colombel J.F, Lassmann H, Desreumaux P& Liblau R.S . 2001Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease?. Proc. Natl Acad. Sci. USA. 98, 13 306–13 311.doi:10.1073/pnas.231474098. . Crossref, ISI, Google ScholarCserr H.F& Knopf P.M . 1992Cervical lymphatics, the blood–brain barrier and the immunoreactivity of the brain: a new view. Immunol. Today. 13, 507–512.doi:10.1016/0167-5699(92)90027-5. . Crossref, PubMed, Google ScholarCserr H.F& Knopf P.M Cervical lymphatics, the blood–brain barrier, and the immunoreactivity of the brain. Immunology of the nervous system, Keane R.W& Hickey W.F . 1997pp. 134–152. Eds. Oxford:Oxford University Press. Google ScholarCserr H.F, DePasquale M, Harling-Berg C.J, Park J.T& Knopf P.M . 1992Afferent and efferent arms of the humoral immune response to CSF-administered albumins in a rat model with normal blood–brain barrier permeability. J. Neuroimmunol. 41, 195–202.doi:10.1016/0165-5728(92)90070-2. . Crossref, PubMed, ISI, Google ScholarDate I, Kawamura K, Nakashima H, Ono K& Nishimoto A . 1988Intraparenchymal allografts in the mouse brain in relation to immunocytochemical identification of T lymphocyte subsets. Neurosci. Lett. 86, 17–20.doi:10.1016/0304-3940(88)90175-9. . Crossref, PubMed, ISI, Google ScholarDickson D.W, Lee S.C, Mattiace L.A, Yen S.H& Brosnan C . 1993Microglia and cytokines in neurological disease, with special reference to AIDS and Alzheimer's disease. Glia. 7, 75–83.doi:10.1002/glia.440070113. . Crossref, PubMed, ISI, Google ScholarDrukker M& Benvenisty N . 2004The immunogenicity of human embryonic stem-derived cells. Trends Biotechnol. 22, 136–141.doi:10.1016/j.tibtech.2004.01.003. . Crossref, PubMed, ISI, Google ScholarDrukker M, Katz G, Urbach A, Schuldiner M, Markel G, Itskovitz-Eldor J, Reubinoff B, Mandelboim O& Benvenisty N . 2002Characterization of the expression of MHC proteins in human embryonic stem cells. Proc. Natl Acad. Sci. USA. 99, 9864–9869.doi:10.1073/pnas.142298299. . Crossref, PubMed, ISI, Google ScholarDuBois J.H, Hammond-Tooke G.D& Cuzner M.L . 1985Expression of major histocompatibility complex antigens in neonate rat primary mixed glial cultures. J. Neuroimmunol. 9, 363–377.doi:10.1016/S0165-5728(85)80036-9. . Crossref, PubMed, ISI, Google ScholarDuncan I.D, Hammang J.P& Jackson K.F . 1987Myelin mosaicism in female heterozygotes of the canine shaking pup and myelin-deficient rat mutants. Brain Res. 402, 168–172.doi:10.1016/0006-8993(87)91062-6. . Crossref, PubMed, ISI, Google ScholarDuncan I.D, Lunn K.F, Holmgren B, Urba-Holmgren R& Brignolo-Holmes L . 1992The taiep rat: a myelin mutant with an associated oligodendrocyte microtubular defect. J. Neurocytol. 21, 870–884.doi:10.1007/BF01191684. . Crossref, PubMed, Google ScholarEspinosa de los Monteros A, Bernard R, Tiller B, Rouget P& de Vellis J . 1993Grafting of fast blue labeled glial cells into neonatal rat brain: differential survival and migration among cell types. Int. J. Dev. Neurosci. 11, 625–639.doi:10.1016/0736-5748(93)90051-E. . Crossref, PubMed, ISI, Google ScholarEspinosa de los Monteros A, Baba H, Zhao P.M, Pan T, Chang R, de Vellis J& Ikenaka K . 2001Remyelination of the adult demyelinated mouse brain by grafted oligodendrocyte progenitors and the effect of B-104 cografts. Neurochem. Res. 26, 673–682.doi:10.1023/A:1010943505013. . Crossref, PubMed, ISI, Google ScholarFarkas-Bargeton E, Robain O& Mandel P . 1972Abnormal glial maturation in the white matter in Jimpy mice. An optical study. Acta Neuropathol. (Berl.). 21, 272–281.doi:10.1007/BF00685135. . Crossref, PubMed, ISI, Google ScholarFinsen B.R, Sorensen T, Castellano B, Pedersen E.B& Zimmer J . 1991Leukocyte infiltration and glial reactions in xenografts of mouse brain tissue undergoing rejection in the adult rat brain. A light and electron microscopical immunocytochemical study. J. Neuroimmunol. 32, 159–183.doi:10.1016/0165-5728(91)90008-U. . Crossref, PubMed, ISI, Google ScholarFinsen B.R, Jorgensen M.B, Diemer N.H& Zimmer J . 1993Microglial MHC antigen expression after ischemic and kainic acid lesions of the adult rat hippocampus. Glia. 7, 41–49.doi:10.1002/glia.440070109. . Crossref, PubMed, ISI, Google ScholarFischer H.G& Reichmann G . 2001Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J. Immunol. 166, 2717–2726. Crossref, PubMed, ISI, Google ScholarFischer H.G, Bonifas U& Reichmann G . 2000Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii. J. Immunol. 164, 4826–4834. Crossref, PubMed, ISI, Google ScholarFontana A, Fierz W& Wekerle H . 1984Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature. 307, 273–276.doi:10.1038/307273a0. . Crossref, PubMed, ISI, Google ScholarFoote A.K& Blakemore W.F Inflammation stimulates remyelination in areas of chronic demyelination. Brain. 128, 2005a528–539.doi:10.1093/brain/awh417. . Crossref, PubMed, ISI, Google ScholarFoote A.K& Blakemore W.F Repopulation of oligodendrocyte progenitor cell depleted tissue in a model of chronic demyelination. Neuropathol. Appl. Neurobiol. 31, 2005b105–114.doi:10.1111/j.1365-2990.2004.00634.x. . Crossref, PubMed, ISI, Google ScholarFranklin R.J Remyelination of the demyelinated CNS: the case for and against transplantation of central, peripheral and olfactory glia. Brain Res. Bull. 57, 2002a827–832.doi:10.1016/S0361-9230(01)00765-1. . Crossref, PubMed, ISI, Google ScholarFranklin R.J Why does remyelination fail in multiple sclerosis?. Nat. Rev. Neurosci. 3, 2002b705–714.doi:10.1038/nrn917. . Crossref, PubMed, ISI, Google ScholarFranklin R.J, Bayley S.A, Milner R, Ffrench-Constant C& Blakemore W.F . 1995Differentiation of the O-2A progenitor cell line CG-4 into oligodendrocytes and astrocytes following transplantation into glia-deficient areas of CNS white matter. Glia. 13, 39–44.doi:10.1002/glia.440130105. . Crossref, PubMed, ISI, Google ScholarFrei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C& Fontana A . 1987Antigen presentation and tumor cytotoxicity by interferon-gamma-treated microglial cells. Eur. J. Immunol. 17, 1271–1278. Crossref, PubMed, ISI, Google ScholarFriedrich V.L& Lazzarini R.A . 1993Restricted migration of transplanted oligodendrocytes or their progenitors, revealed by transgenic marker M beta P. J. Neural. Transplant. Plast. 4, 139–146. Crossref, PubMed, ISI, Google ScholarGansmuller A, Clerin E, Kruger F, Gumpel M& Lachapelle F . 1991Tracing transplanted oligodendrocytes during migration and maturation in the shiverer mouse brain. Glia. 4, 580–590.doi:10.1002/glia.440040605. . Crossref, PubMed, ISI, Google ScholarGobin S.J, Montagne L, Van Zutphen M, Van Der Valk P, Van Den Elsen P.J& De Groot C.J . 2001Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions. Glia. 36, 68–77.doi:10.1002/glia.1096. . Crossref, PubMed, ISI, Google ScholarGordon L.B, Nolan S.C, Cserr H.F, Knopf P.M& Harling-Berg C.J . 1997Growth of P511 mastocytoma cells in BALB/c mouse brain elicits CTL response without tumor elimination: a new tumor model for regional central nervous system immunity. J. Immunol. 159, 2399–2408. PubMed, ISI, Google ScholarGordon L.B, Nolan S.C, Ksander B.R, Knopf P.M& Harling-Berg C.J . 1998Normal cerebrospinal fluid suppresses the in vitro development of cytotoxic T cells: role of the brain microenvironment in CNS immune regulation. J. Neuroimmunol. 88, 77–84.doi:10.1016/S0165-5728(98)00077-0. . Crossref, PubMed, ISI, Google ScholarGout O, Gansmuller A, Baumann N& Gumpel M . 1988Remyelination by transplanted oligodendrocytes of a demyelinated lesion in the spinal cord of the adult shiverer mouse. Neurosci. Lett. 87, 195–199.doi:10.1016/0304-3940(88)90169-3. . Crossref, PubMed, ISI, Google ScholarGrenier Y, Ruijs T.C, Robitaille Y, Olivier A& Antel J.P . 1989Immunohistochemical studies of adult human glial cells. J. Neuroimmunol. 21, 103–115.doi:10.1016/0165-5728(89)90166-5. . Crossref, PubMed, ISI, Google ScholarHamilton J.A, Byrne R& Whitty G . 2000Particulate adjuvants can induce macrophage survival, DNA synthesis, and a synergistic proliferative response to GM-CSF and CSF-1. J. Leukoc. Biol. 67, 226–232. Crossref, PubMed, ISI, Google ScholarHarling-Berg C, Knopf P.M, Merriam J& Cserr H.F . 1989Role of cervical lymph nodes in the systemic humoral immune response to human serum albumin microinfused into rat cerebrospinal fluid. J. Neuroimmunol. 25, 185–193.doi:10.1016/0165-5728(89)90136-7. . Crossref, PubMed, ISI, Google ScholarHarling-Berg C.J, Park T.J& Knopf P.M . 1999Role of the cervical lymphatics in the Th2-type hierarchy of CNS immune regulation. J. Neuroimmunol. 101, 111–127.doi:10.1016/S0165-5728(99)00130-7. . Crossref, PubMed, ISI, Google ScholarHarvey A.R, Fan Y, Beilharz M.W& Grounds M.D . 1992Survival and migration of transplanted male glia in adult female mouse brains monitored by a Y-chromosome-specific probe. Brain Res. Mol. Brain Res. 12, 339–343.doi:10.1016/0169-328X(92)90137-Z. . Crossref, PubMed, Google ScholarHead J.R& Griffin W.S . 1985Functional capacity of solid tissue transplants in the brain: evidence for immunological privilege. Proc. R. Soc. B. 224, 375–387. Link, ISI, Google ScholarHeath W.R& Carbone F.R . 2001Cross-presentation, dendritic cells, tolerance and immunity. Annu. Rev. Immunol. 19, 47–64.doi:10.1146/annurev.immunol.19.1.47. . Crossref, PubMed, ISI, Google ScholarHerrera J, Yang H, Zhang S.C, Proschel C, Tresco P, Duncan I.D, Luskin M& Mayer-Proschel M . 2001Embryonic-derived glial-restricted precursor cells (GRP cells) can differentiate into astrocytes and oligodendrocytes in vivo. Exp. Neurol. 171, 11–21.doi:10.1006/exnr.2001.7729. . Crossref, PubMed, ISI, Google ScholarHickey W.F . 1999Leukocyte traffic in the central nervous system: the participants and their roles. Semin. Immunol. 11, 125–137.doi:10.1006/smim.1999.0168. . Crossref, PubMed, ISI, Google ScholarHickey W.F& Kimura H . 1988Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 239, 290–292. Crossref, PubMed, ISI, Google ScholarHickey W.F, Osborn J.P& Kirby W.M . 1985Expression of Ia molecules by astrocytes during acute experimental allergic encephalomyelitis in the Lewis rat. Cell. Immunol. 91, 528–535.doi:10.1016/0008-8749(85)90251-5. . Crossref, PubMed, ISI, Google ScholarHickey W.F, Hsu B.L& Kimura H . 1991T-lymphocyte entry into the central nervous system. J. Neurosci. Res. 28, 254–260.doi:10.1002/jnr.490280213. . Crossref, PubMed, ISI, Google ScholarHickey W.F, Vass K& Lassmann H . 1992Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. J. Neuropathol. Exp. Neurol. 51, 246–256. Crossref, PubMed, ISI, Google ScholarHinks G.L, Chari D.M, O'Leary M.T, Zhao C, Keirstead H.S, Blakemore W.F& Franklin R.J . 2001Depletion of endogenous oligodendrocyte progenitors rather than increased availability of survival factors is a likely explanation for enhanced survival of transplanted oligodendrocyte progenitors in X-irradiated compared to normal CNS. Neuropathol. Appl. Neurobiol. 27, 59–67.doi:10.1046/j.0305-1846.2001.00303.x. . Crossref, PubMed, ISI, Google ScholarHofman F.M, von Hanwehr R.I, Dinarello C.A, Mizel S.B, Hinton D& Merrill J.E . 1986Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain. J. Immunol. 136, 3239–3245. PubMed, ISI, Google ScholarHohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H& Wekerle H . 2000The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J. Neuroimmunol. 107, 161–166.doi:10.1016/S0165-5728(00)00233-2. . Crossref, PubMed, ISI, Google ScholarHolda J.H, Welch A.M& Swanborg R.H . 1980Autoimmune effector cells. I. Transfer of experimental encephalomyelitis with lymphoid cells cultured with antigen. Eur. J. Immunol. 10, 657–659. Crossref, PubMed, ISI, Google ScholarHonmou O, Felts P.A, Waxman S.G& Kocsis J.D . 1996Restoration of normal conduction properties in demyelinated spinal cord axons in the adult rat by transplantation of exogenous Schwann cells. J. Neurosci. 16, 3199–3208. Crossref, PubMed, ISI, Google ScholarIkenaka K& Kagawa T . 1995Transgenic systems in studying myelin gene expression. Dev. Neurosci. 17, 127–136. Crossref, PubMed, ISI, Google ScholarImitola J, Snyder E.Y& Khoury S.J . 2003Genetic programs and responses of neural stem/progenitor cells during demyelination: potential insights into repair mechanisms in multiple sclerosis. Physiol. Genomics. 14, 171–197. Crossref, PubMed, ISI, Google ScholarIsono M, Poltorak M, Kulaga H, Adams A.J& Freed W.J . 1993Certain host–donor strain combinations do not reject brain allografts after systemic sensitization. Exp. Neurol. 122, 48–56.doi:10.1006/exnr.1993.1106. . Crossref, PubMed, ISI, Google ScholarIwashita Y, Crang A.J& Blakemore W.F . 2000Redistribution of bisbenzimide Hoechst 33342 from transplanted cells to host cells. Neuroreport. 11, 1013–1016. Crossref, PubMed, ISI, Google ScholarKagawa T, 1994Glial cell degeneration and hypomyelination caused by overexpression of myelin proteolipid protein gene. Neuron. 13, 427–442.doi:10.1016/0896-6273(94)90358-1. . Crossref, PubMed, ISI, Google ScholarKarman J, Ling C, Sandor M& Fabry Z . 2004Dendritic cells in the initiation of immune responses against central nervous system-derived antigens. Immunol. Lett. 92, 107–115.doi:10.1016/j.imlet.2003.10.017. . Crossref, PubMed, ISI, Google ScholarKida S, Steart P.V, Zhang E.T& Weller R.O . 1993Perivascular cells act as scavengers in the cerebral perivascular spaces and remain distinct from pericytes, microglia and macrophages. Acta Neuropathol. (Berl.). 85, 646–652.doi:10.1007/BF00334675. . Crossref, PubMed, ISI, Google ScholarKida S, Weller R.O, Zhang E.T, Phillips M.J& Iannotti F . 1995Anatomical pathways for lymphatic drainage of the brain and their pathological significance. Neuropathol. Appl. Neurobiol. 21, 181–184. Crossref, PubMed, ISI, Google ScholarKurkowska-Jastrzebska I, Wronska A, Kohutnicka M, Czlonkowski A& Czlonkowska A . 1999MHC class II positive microglia and lymphocytic infiltration are present in the substantia nigra and striatum in mouse model of Parkinson's disease. Acta Neurobiol. Exp. (Warsz). 59, 1–8. PubMed, ISI, Google ScholarLachapelle F, Duhamel-Clerin E, Gansmuller A, Baron-Van Evercooren A, Villarroya H& Gumpel M . 1994Transplanted transgenically marked oligodendrocytes survive, migrate and myelinate in the normal mouse brain as they do in the shiverer mouse brain. Eur. J. Neurosci. 6, 814–824. Crossref, PubMed, ISI, Google ScholarLakatos A, Franklin R.J& Barnett S.C . 2000Olfactory ensheathing cells and Schwann cells differ in their in vitro interactions with astrocytes. Glia. 32, 214–225.doi:10.1002/1098-1136(200012)32:3<214::AID-GLIA20>3.0.CO;2-7. . Crossref, PubMed, ISI, Google ScholarLakatos A, Barnett S.C& Franklin R.J . 2003Olfactory ensheathing cells induce less host astrocyte response and chondroitin sulphate proteoglycan expression than Schwann cells following transplantation into adult CNS white matter. Exp. Neurol. 184, 237–246.doi:10.1016/S0014-4886(03)00270-X. . Crossref, PubMed, ISI, Google ScholarLampson L.A . 1987Molecular bases of the immune response to neural antigens. Trends Neurosci. 10, 211–216.doi:10.1016/0166-2236(87)90153-6. . Crossref, ISI, Google ScholarLampson L.A& Hickey W.F . 1986Monoclonal antibody analysis of MHC expression in human brain biopsies: tissue ranging from “histologically normal” to that showing different levels of glial tumor involvement. J. Immunol. 136, 4054–4062. PubMed, ISI, Google ScholarLassmann H Cellular damage and repair in multiple sclerosis. Myelin biology and disorders& Lazzarini R.A vol. 22004pp. 733–762. Eds. USA:Elsevier. Google ScholarLassmann H& Ransohoff R.M . 2004The CD4-Th1 model for multiple sclerosis: a critical [correction of crucial] re-appraisal. Trends Immunol. 25, 132–137.doi:10.1016/j.it.2004.01.007. . Crossref, PubMed, ISI, Google ScholarLassmann H, Zimprich F, Vass K& Hickey W.F . 1991Microglial cells are a component of the perivascular glia limitans. J. Neurosci. Res. 28, 236–243.doi:10.1002/jnr.490280211. . Crossref, PubMed, ISI, Google ScholarLawrence J.M, Morris R.J, Wilson D.J& Raisman G . 1990Mechanisms of allograft rejection in the rat brain. Neuroscience. 37, 431–462.doi:10.1016/0306-4522(90)90413-X. . Crossref, PubMed, ISI, Google ScholarLee S.C, Moore G.R, Golenwsky G& Raine C.S . 1990Multiple sclerosis: a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study. J. Neuropathol. Exp. Neurol. 49, 122–136. Crossref, PubMed, ISI, Google ScholarLee S.C, Collins M, Vanguri P& Shin M.L . 1992Glutamate differentially inhibits the expression of class II MHC antigens on astrocytes and microglia. J. Immunol. 148, 3391–3397. PubMed, ISI, Google ScholarLevine S . 1970Allergic encephalomyelitis: cellular transformation and vascular blockade. J. Neuropathol. Exp. Neurol. 29, 6–20. Crossref, PubMed, ISI, Google ScholarLi D.W& Duncan I.D . 1998The immune status of the myelin deficient rat and its immune responses to transplanted allogeneic glial cells. J. Neuroimmunol. 85, 202–211.doi:10.1016/S0165-5728(98)00006-X. . Crossref, PubMed, ISI, Google ScholarLi Y.Q, Chen P, Jain V, Reilly R.M& Wong C.S . 2004Early radiation-induced endothelial cell loss and blood–spinal cord barrier breakdown in the rat spinal cord. Radiat. Res. 161, 143–152. Crossref, PubMed, ISI, Google ScholarLinda H, Hammarberg H, Cullheim S, Levinovitz A, Khademi M& Olsson T . 1998Expression of MHC class I and beta2-microglobulin in rat spinal motoneurons: regulatory influences by IFN-gamma and axotomy. Exp. Neurol. 150, 282–295. Crossref, PubMed, ISI, Google ScholarLove S, Wiley C.A, Fujinami R.S& Lampert P.W . 1987Effects of regional spinal X-irradiation on demyelinating disease caused by Theiler's virus, mouse hepatitis virus or experimental allergic encephalomyelitis. J. Neuroimmunol. 14, 19–33.doi:10.1016/0165-5728(87)90098-1. . Crossref, PubMed, ISI, Google ScholarLowhagen P, Johansson B.B& Nordborg C . 1994The nasal route of cerebrospinal fluid drainage in man. A light-microscope study. Neuropathol. Appl. Neurobiol. 20, 543–550. Crossref, PubMed, ISI, Google ScholarLucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M& Lassmann H . 2000Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47, 707–717.doi:10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q. . Crossref, PubMed, ISI, Google ScholarMason D.W, Charlton H.M, Jones A.J, Lavy C.B, Puklavec M& Simmonds S.J . 1986The fate of allogeneic and xenogeneic neuronal tissue transplanted into the third ventricle of rodents. Neuroscience. 19, 685–694.doi:10.1016/0306-4522(86)90292-7. . Crossref, PubMed, ISI, Google ScholarMassa P.T, ter Meulen V& Fontana A . 1987Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA. 84, 4219–4223. Crossref, PubMed, ISI, Google ScholarMassa P.T, Ozato K& McFarlin D.E . 1993Cell type-specific regulation of major histocompatibility complex (MHC) class I gene expression in astrocytes, oligodendrocytes, and neurons. Glia. 8, 201–207.doi:10.1002/glia.440080307. . Crossref, PubMed, ISI, Google ScholarMato M, 1996Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex. Proc. Natl Acad. Sci. USA. 93, 3269–3274.doi:10.1073/pnas.93.8.3269. . Crossref, PubMed, ISI, Google ScholarMatsumoto Y, Kawai K& Fujiwara M . 1989In situ Ia expression on brain cells in the rat: autoimmune encephalomyelitis-resistant strain (BN) and susceptible strain (Lewis) compared. Immunology. 66, 621–627. PubMed, ISI, Google ScholarMatsumoto Y, Kohyama K, Aikawa Y, Shin T, Kawazoe Y, Suzuki Y& Tanuma N . 1998Role of natural killer cells and TCR gamma delta T cells in acute autoimmune encephalomyelitis. Eur. J. Immunol. 28, 1681–1688.doi:10.1002/(SICI)1521-4141(199805)28:05<1681::AID-IMMU1681>3.0.CO;2-T. . Crossref, PubMed, ISI, Google ScholarMatyszak M.K& Perry V.H . 1996The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system. Neuroscience. 74, 599–608.doi:10.1016/0306-4522(96)00160-1. . Crossref, PubMed, ISI, Google ScholarMatyszak M.K, Lawson L.J, Perry V.H& Gordon S . 1992Stromal macrophages of the choroid plexus situated at an interface between the brain and peripheral immune system constitutively express major histocompatibility class II antigens. J. Neuroimmunol. 40, 173–181.doi:10.1016/0165-5728(92)90131-4. . Crossref, PubMed, ISI, Google ScholarMauerhoff T, Pujol-Borrell R, Mirakian R& Bottazzo G.F . 1988Differential expression and regulation of major histocompatibility complex (MHC) products in neural and glial cells of the human fetal brain. J. Neuroimmunol. 18, 271–289.doi:10.1016/0165-5728(88)90049-5. . Crossref, PubMed, ISI, Google ScholarMcLaren F.H, Svendsen C.N, Van der Meide P& Joly E . 2001Analysis of neural stem cells by flow cytometry: cellular differentiation modifies patterns of MHC expression. J. Neuroimmunol. 112, 35–46.doi:10.1016/S0165-5728(00)00410-0. . Crossref, PubMed, ISI, Google ScholarMcMenamin P.G . 1999Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations. J. Comp. Neurol. 405, 553–562.doi:10.1002/(SICI)1096-9861(19990322)405:4<553::AID-CNE8>3.0.CO;2-6. . Crossref, PubMed, ISI, Google ScholarMedawar P.B . 1948Immunity to homologous grafted skin. III. Fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. Br. J. Exp. 29, 58–69. PubMed, Google ScholarMucke L& Oldstone M.B . 1992The expression of major histocompatibility complex (MHC) class I antigens in the brain differs markedly in acute and persistent infections with lymphocytic choriomeningitis virus (LCMV). J. Neuroimmunol. 36, 193–198.doi:10.1016/0165-5728(92)90050-U. . Crossref, PubMed, ISI, Google ScholarMurphy J.B& Sturm E . 1923Conditions determining the transplantability of tissues in the brain. J. Exp. Med. 38, 183–197.doi:10.1084/jem.38.2.183. . Crossref, PubMed, Google ScholarNicholas M.K, Antel J.P, Stefansson K& Arnason B.G . 1987Rejection of fetal neocortical neural transplants by H-2 incompatible mice. J. Immunol. 139, 2275–2283. PubMed, ISI, Google ScholarNikcevich K.M, Piskurich J.F, Hellendall R.P, Wang Y& Ting J.P . 1999Differential selectivity of CIITA promoter activation by IFN-gamma and IRF-1 in astrocytes and macrophages: CIITA promoter activation is not affected by TNF-alpha. J. Neuroimmunol. 99, 195–204.doi:10.1016/S0165-5728(99)00117-4. . Crossref, PubMed, ISI, Google ScholarOgura K, Ogawa M& Yoshida M . 1994Effects of ageing on microglia in the normal rat brain: immunohistochemical observations. Neuroreport. 5, 1224–1226. Crossref, PubMed, ISI, Google ScholarO'Leary M.T& Blakemore W.F . 1997Use of a rat Y chromosome probe to determine the long-term survival of glial cells transplanted into areas of CNS demyelination. J. Neurocytol. 26, 191–206.doi:10.1023/A:1018536130578. . Crossref, PubMed, Google ScholarOlsson T, Maehlen J, Love A, Klareskog L, Norrby E& Kristensson K . 1987Induction of class I and class II transplantation antigens in rat brain during fatal and non-fatal measles virus infection. J. Neuroimmunol. 16, 215–224.doi:10.1016/0165-5728(87)90076-2. . Crossref, PubMed, ISI, Google ScholarPanitch H.S . 1980Adoptive transfer of experimental allergic encephalomyelitis with activated spleen cells: comparison of in vitro activation by concanavalin a and myelin basic protein. Cell. Immunol. 56, 163–171.doi:10.1016/0008-8749(80)90091-X. . Crossref, PubMed, ISI, Google ScholarPashenkov M, Huang Y.M, Kostulas V, Haglund M, Soderstrom M& Link H . 2001Two subsets of dendritic cells are present in human cerebrospinal fluid. Brain. 124, 480–492.doi:10.1093/brain/124.3.480. . Crossref, PubMed, ISI, Google ScholarPashenkov M, Teleshova N, Kouwenhoven M, Kostulas V, Huang Y.M, Soderstrom M& Link H . 2002Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple sclerosis and acute optic neuritis. Clin. Exp. Immunol. 127, 519–526.doi:10.1046/j.1365-2249.2002.01779.x. . Crossref, PubMed, ISI, Google ScholarPerry V.H& Lund R.D . 1989Microglia in retinae transplanted to the central nervous system. Neuroscience. 31, 453–462.doi:10.1016/0306-4522(89)90387-4. . Crossref, PubMed, ISI, Google ScholarPersidsky Y, Stins M, Way D, Witte M.H, Weinand M, Kim K.S, Bock P, Gendelman H.E& Fiala M . 1997A model for monocyte migration through the blood–brain barrier during HIV-1 encephalitis. J. Immunol. 158, 3499–3510. PubMed, ISI, Google ScholarPluchino S, 2003Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature. 422, 688–694.doi:10.1038/nature01552. . Crossref, PubMed, ISI, Google ScholarPoltorak M& Freed W.J . 1989Immunological reactions induced by intracerebral transplantation: evidence that host microglia but not astroglia are the antigen-presenting cells. Exp. Neurol. 103, 222–233.doi:10.1016/0014-4886(89)90046-0. . Crossref, PubMed, ISI, Google ScholarPoltorak M& Freed W.J Transplantation into the central nervous system. Immunology of the nervous system, Hickey W.F& Keane R.W . 1997pp. 611–641. Eds. Oxford:Oxford University Press. Google ScholarRaju S& Grogan J.B . 1977Immunologic study of the brain as a privileged site. Transplant. Proc. 9, 1187–1191. PubMed, ISI, Google ScholarRosenzweig M, Connole M, Glickman R, Yue S.P, Noren B, DeMaria M& Johnson R.P . 2001Induction of cytotoxic T lymphocyte and antibody responses to enhanced green fluorescent protein following transplantation of transduced CD34(+) hematopoietic cells. Blood. 97, 1951–1959.doi:10.1182/blood.V97.7.1951. . Crossref, PubMed, ISI, Google ScholarSatoh J, Kim S.U, Kastrukoff L.F& Takei F . 1991Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes. J. Neurosci. Res. 29, 1–12.doi:10.1002/jnr.490290102. . Crossref, PubMed, ISI, Google ScholarSatoh J, Paty D.W& Kim S.U . 1995Differential effects of beta and gamma interferons on expression of major histocompatibility complex antigens and intercellular adhesion molecule-1 in cultured fetal human astrocytes. Neurology. 45, 367–373. Crossref, PubMed, ISI, Google ScholarScheinberg L.C, Kotsilimbas D.G, Karpf R& Mayer N . 1966Is the brain “an immunologically privileged site”? 3. Studies based on homologous skin grafts to the brain and subcutaneous tissues. Arch. Neurol. 15, 62–67. Crossref, PubMed, Google ScholarSchmied M, Breitschopf H, Gold R, Zischler H, Rothe G, Wekerle H& Lassmann H . 1993Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am. J. Pathol. 143, 446–452. PubMed, ISI, Google ScholarSchwartz M& Cohen I.R . 2000Autoimmunity can benefit self-maintenance. Immunol. Today. 21, 265–268.doi:10.1016/S0167-5699(00)01633-9. . Crossref, PubMed, Google ScholarScott D.M, Ehrmann I.E, Ellis P.S, Chandler P.R& Simpson E . 1997Why do some females reject males? The molecular basis for male-specific graft rejection. J. Mol. Med. 75, 103–114.doi:10.1007/s001090050095. . Crossref, PubMed, ISI, Google ScholarSeabrook T.J, Johnston M& Hay J.B . 1998Cerebral spinal fluid lymphocytes are part of the normal recirculating lymphocyte pool. J. Neuroimmunol. 91, 100–107.doi:10.1016/S0165-5728(98)00164-7. . Crossref, PubMed, ISI, Google ScholarSeabrook T, Au B, Dickstein J, Zhang X, Ristevski B& Hay J.B . 1999The traffic of resting lymphocytes through delayed hypersensitivity and chronic inflammatory lesions: a dynamic equilibrium. Semin. Immunol. 11, 115–123.doi:10.1006/smim.1999.0167. . Crossref, PubMed, ISI, Google ScholarSedgwick J.D& Hickey W.F Antigen presentation in the central nervous system. Immunology of the nervous system, Keane R.W& Hickey W.F . 1997pp. 364–418. Eds. Oxford:Oxford University Press. Google ScholarSerafini B, Columba-Cabezas S, Di Rosa F& Aloisi F . 2000Intracerebral recruitment and maturation of dendritic cells in the onset and progression of experimental autoimmune encephalomyelitis. Am. J. Pathol. 157, 1991–2002. Crossref, PubMed, ISI, Google ScholarSheffield L.G& Berman N.E . 1998Microglial expression of MHC class II increases in normal aging of nonhuman primates. Neurobiol. Aging. 19, 47–55.doi:10.1016/S0197-4580(97)00168-1. . Crossref, PubMed, ISI, Google ScholarSimpson E, Scott D& Chandler P . 1997The male-specific histocompatibility antigen, H-Y: a history of transplantation, immune response genes, sex determination and expression cloning. Annu. Rev. Immunol. 15, 39–61.doi:10.1146/annurev.immunol.15.1.39. . Crossref, PubMed, ISI, Google ScholarSloan D.J, Baker B.J, Puklavec M& Charlton H.M . 1990The effect of site of transplantation and histocompatibility differences on the survival of neural tissue transplanted to the CNS of defined inbred rat strains. Prog. Brain Res. 82, 141–152. Crossref, PubMed, ISI, Google ScholarSmith P.M& Blakemore W.F . 2000Porcine neural progenitors require commitment to the oligodendrocyte lineage prior to transplantation in order to achieve significant remyelination of demyelinated lesions in the adult CNS. Eur. J. Neurosci. 12, 2414–2424.doi:10.1046/j.1460-9568.2000.00137.x. . Crossref, PubMed, ISI, Google ScholarSteiniger B& van der Meide P.H . 1988Rat ependyma and microglia cells express class II MHC antigens after intravenous infusion of recombinant gamma interferon. J. Neuroimmunol. 19, 111–118.doi:10.1016/0165-5728(88)90040-9. . Crossref, PubMed, ISI, Google ScholarSteinman R.M& Nussenzweig M.C . 2002Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl Acad. Sci. USA. 99, 351–358.doi:10.1073/pnas.231606698. . Crossref, PubMed, ISI, Google ScholarStewart P.A, Vinters H.V& Wong C.S . 1995Blood–spinal cord barrier function and morphometry after single doses of x-rays in rat spinal cord. Int. J. Radiat. Oncol. Biol. Phys. 32, 703–711.doi:10.1016/0360-3016(94)00594-B. . Crossref, PubMed, ISI, Google ScholarStreilein J.W . 1987Immune regulation and the eye: a dangerous compromise. FASEB J. 1, 199–208. Crossref, PubMed, ISI, Google ScholarStreilein J.W . 2003Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat. Rev. Immunol. 3, 879–889.doi:10.1038/nri1224. . Crossref, PubMed, ISI, Google ScholarStreilein J.W& Niederkorn J.Y . 1981Induction of anterior chamber-associated immune deviation requires an intact, functional spleen. J. Exp. Med. 153, 1058–1067.doi:10.1084/jem.153.5.1058. . Crossref, PubMed, ISI, Google ScholarStreilein J.W& Taylor A.W Immunologic principles related to the nervous system and the eye. Immunology of the nervous system, Hickey W.F& Keane R.W . 1997pp. 99–133. Eds. Oxford:Oxford University Press. Google ScholarStripecke R, Carmen V.M, Skelton D, Satake N, Halene S& Kohn D . 1999Immune response to green fluorescent protein: implications for gene therapy. Gene Ther. 6, 1305–1312.doi:10.1038/sj.gt.3300951. . Crossref, PubMed, ISI, Google ScholarSuter T, Malipiero U, Otten L, Ludewig B, Muelethaler-Mottet A, Mach B, Reith W& Fontana A . 2000Dendritic cells and differential usage of the MHC class II transactivator promoters in the central nervous system in experimental autoimmune encephalitis. Eur. J. Immunol. 30, 794–802.doi:10.1002/1521-4141(200003)30:3<794::AID-IMMU794>3.0.CO;2-Q. . Crossref, PubMed, ISI, Google ScholarSuter T, Biollaz G, Gatto D, Bernasconi L, Herren T, Reith W& Fontana A . 2003The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation. Eur. J. Immunol. 33, 2998–3006.doi:10.1002/eji.200323611. . Crossref, PubMed, ISI, Google ScholarSuzumura A& Silberberg D.H . 1985Expression of H-2 antigen on oligodendrocytes is induced by soluble factors from concanavalin A activated T cells. Brain Res. 336, 171–175.doi:10.1016/0006-8993(85)90431-7. . Crossref, PubMed, ISI, Google ScholarSuzumura A, Silberberg D.H& Lisak R.P The expression of MHC antigens on oligodendrocytes: induction of polymorphic H-2 expression by lymphokines. J. Neuroimmunol. 11, 1986a179–190.doi:10.1016/0165-5728(86)90002-0. . Crossref, PubMed, ISI, Google ScholarSuzumura A, Lavi E, Weiss S.R& Silberberg D.H Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes. Science. 232, 1986b991–993. Crossref, PubMed, ISI, Google ScholarSuzumura A, Mezitis S.G, Gonatas N.K& Silberberg D.H . 1987MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by gamma-interferon. J. Neuroimmunol. 15, 263–278.doi:10.1016/0165-5728(87)90121-4. . Crossref, PubMed, ISI, Google ScholarTontsch U, Archer D.R, Dubois-Dalcq M& Duncan I.D . 1994Transplantation of an oligodendrocyte cell line leading to extensive myelination. Proc. Natl Acad. Sci. USA. 91, 11 616–11 620. Crossref, ISI, Google ScholarTourbah A, Linnington C, Bachelin C, Avellana-Adalid V, Wekerle H& Baron-Van Evercooren A . 1997Inflammation promotes survival and migration of the CG4 oligodendrocyte progenitors transplanted in the spinal cord of both inflammatory and demyelinated EAE rats. J. Neurosci. Res. 50, 853–861.doi:10.1002/(SICI)1097-4547(19971201)50:5<853::AID-JNR21>3.0.CO;2-0. . Crossref, PubMed, ISI, Google ScholarTraugott U . 1987Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J. Neuroimmunol. 16, 283–302.doi:10.1016/0165-5728(87)90082-8. . Crossref, PubMed, ISI, Google ScholarTraugott U, McFarlin D.E& Raine C.S . 1986Immunopathology of the lesion in chronic relapsing experimental autoimmune encephalomyelitis in the mouse. Cell. Immunol. 99, 395–410.doi:10.1016/0008-8749(86)90248-0. . Crossref, PubMed, ISI, Google ScholarTurnley A.M, Miller J.F& Bartlett P.F . 1991Regulation of MHC molecules on MBP positive oligodendrocytes in mice by IFN-gamma and TNF-alpha. Neurosci. Lett. 123, 45–48.doi:10.1016/0304-3940(91)90154-L. . Crossref, PubMed, ISI, Google ScholarVass K& Lassmann H . 1990Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system. Am. J. Pathol. 137, 789–800. PubMed, ISI, Google ScholarVass K, Lassmann H, Wekerle H& Wisniewski H.M . 1986The distribution of Ia antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol. (Berl.). 70, 149–160.doi:10.1007/BF00691433. . Crossref, PubMed, ISI, Google ScholarWagers A.J, Sherwood R.I, Christensen J.L& Weissman I.L . 2002Little evidence for developmental plasticity of adult hematopoietic stem cells. Science. 297, 2256–2259.doi:10.1126/science.1074807. . Crossref, PubMed, ISI, Google ScholarWeinshenker B.G . 1998The natural history of multiple sclerosis: update 1998. Semin. Neurol. 18, 301–307. Crossref, PubMed, ISI, Google ScholarWeller R.O, Kida S& Zhang E.T . 1992Pathways of fluid drainage from the brain—morphological aspects and immunological significance in rat and man. Brain Pathol. 2, 277–284. Crossref, PubMed, ISI, Google ScholarWenkel H, Streilein J.W& Young M.J . 2000Systemic immune deviation in the brain that does not depend on the integrity of the blood–brain barrier. J. Immunol. 164, 5125–5131. Crossref, PubMed, ISI, Google ScholarWilbanks G.A& Streilein J.W . 1990Distinctive humoral immune responses following anterior chamber and intravenous administration of soluble antigen. Evidence for active suppression of IgG2-secreting B lymphocytes. Immunology. 71, 566–572. PubMed, ISI, Google ScholarWilbanks G.A& Streilein J.W . 1992Fluids from immune privileged sites endow macrophages with the capacity to induce antigen-specific immune deviation via a mechanism involving transforming growth factor-beta. Eur. J. Immunol. 22, 1031–1036. Crossref, PubMed, ISI, Google ScholarWindrem M.S, Roy N.S, Wang J, Nunes M, Benraiss A, Goodman R, McKhann G.M& Goldman S.A . 2002Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain. J. Neurosci. Res. 69, 966–975.doi:10.1002/jnr.10397. . Crossref, PubMed, ISI, Google ScholarWolf S.A, Fisher J, Bechmann I, Steiner B, Kwidzinski E& Nitsch R . 2002Neuroprotection by T-cells depends on their subtype and activation state. J. Neuroimmunol. 133, 72–80.doi:10.1016/S0165-5728(02)00367-3. . Crossref, PubMed, ISI, Google ScholarWong G.H, Bartlett P.F, Clark-Lewis I, Battye F& Schrader J.W . 1984Inducible expression of H-2 and Ia antigens on brain cells. Nature. 310, 688–691.doi:10.1038/310688a0. . Crossref, PubMed, ISI, Google ScholarWong G.H, Bartlett P.F, Clark-Lewis I, McKimm-Breschkin J.L& Schrader J.W . 1985Interferon-gamma induces the expression of H-2 and Ia antigens on brain cells. J. Neuroimmunol. 7, 255–278.doi:10.1016/S0165-5728(84)80026-0. . Crossref, PubMed, ISI, Google ScholarYeager M.P, DeLeo J.A, Hoopes P.J, Hartov A, Hildebrandt L& Hickey W.F . 2000Trauma and inflammation modulate lymphocyte localization in vivo: quantitation of tissue entry and retention using indium-111-labeled lymphocytes. Crit. Care Med. 28, 1477–1482.doi:10.1097/00003246-200005000-00037. . Crossref, PubMed, ISI, Google ScholarZeinstra E, Wilczak N, Streefland C& De Keyser J . 2000Astrocytes in chronic active multiple sclerosis plaques express MHC class II molecules. Neuroreport. 11, 89–91. Crossref, PubMed, ISI, Google ScholarZhang B, Yamamura T, Kondo T, Fujiwara M& Tabira T . 1997Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells. J. Exp. Med. 186, 1677–1687.doi:10.1084/jem.186.10.1677. . Crossref, PubMed, ISI, Google ScholarZigova T, Song S, Willing A.E, Hudson J.E, Newman M.B, Saporta S, Sanchez-Ramos J& Sanberg P.R . 2002Human umbilical cord blood cells express neural antigens after transplantation into the developing rat brain. Cell Transplant. 11, 265–274. Crossref, PubMed, ISI, Google Scholar


