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*
Department of Neurology, and
Division of Clinical Immunology and Rheumatology, University of Alabama, Birmingham, AL 35294;
Department of Immunology, St Jude’s Children’s Research Hospital, Memphis, TN 38105;
Max Planck Institute for Neurobiology, Martinsried, Germany; and
¶ Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, NY 10461
Encephalitogenic T cells that mediate experimental autoimmune
encephalomyelitis (EAE) are commonly assumed to be exclusively
CD4+, but formal proof is still lacking. In this study, we
report that synthetic peptides 35–55 from myelin oligodendrocyte
glycoprotein (pMOG35–55) consistently activate a high
proportion of CD8+ 
TCR+ T cells that are
encephalitogenic in C57BL/6 (B6) mice. The encephalitogenic potential
of CD8+ MOG-specific T cells was established by adoptive
transfer of CD8-enriched MOG-specific T cells. These cells induced a
much more severe and permanent disease than disease actively induced by
immunization with pMOG35–55. CNS lesions in
pMOG35–55 CD8+ T cell-induced EAE were
progressive and more destructive. The CD8+ T cells were
strongly pathogenic in syngeneic B6 and RAG-1-/- mice,
but not in isogeneic 2-microglobulin-deficient mice.
MOG-specific CD8+ T cells could be repeatedly reisolated
for up to 287 days from recipient B6 or RAG-1-/- mice in
which disease was induced adoptively with <1 x 106 T
cells sensitized to pMOG35–55. It is postulated that MOG
induces a relapsing and/or progressive pattern of EAE by eliciting a T
cell response dominated by CD8+ autoreactive T cells. Such
cells appear to have an enhanced tissue-damaging effect and persist in
the animal for long periods.
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S. F. Martin, J. C. Dudda, V. Delattre, E. Bachtanian, C. Leicht, B. Burger, H. U. Weltzien, and J. C. Simon Fas-Mediated Inhibition of CD4+ T Cell Priming Results in Dominance of Type 1 CD8+ T Cells in the Immune Response to the Contact Sensitizer Trinitrophenyl J. Immunol., September 1, 2004; 173(5): 3178 - 3185. [Abstract] [Full Text] [PDF]
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H. Shao, S. L. Sun, H. J. Kaplan, and D. Sun Characterization of Rat CD8+ Uveitogenic T Cells Specific for Interphotoreceptor Retinal-Binding Protein 1177-1191 J. Immunol., August 15, 2004; 173(4): 2849 - 2854. [Abstract] [Full Text] [PDF]
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 M. P. Crawford, S. X. Yan, S. B. Ortega, R. S. Mehta, R. E. Hewitt, D. A. Price, P. Stastny, D. C. Douek, R. A. Koup, M. K. Racke, et al. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay Blood, June 1, 2004; 103(11): 4222 - 4231. [Abstract] [Full Text] [PDF]
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C. Skulina, S. Schmidt, K. Dornmair, H. Babbe, A. Roers, K. Rajewsky, H. Wekerle, R. Hohlfeld, and N. Goebels Multiple sclerosis: Brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood PNAS, February 24, 2004; 101(8): 2428 - 2433. [Abstract] [Full Text] [PDF]
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H. Shao, S. Lei, S. L. Sun, H. J. Kaplan, and D. Sun Conversion of Monophasic to Recurrent Autoimmune Disease by Autoreactive T Cell Subsets J. Immunol., November 15, 2003; 171(10): 5624 - 5630. [Abstract] [Full Text] [PDF]
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 A. Margalit, S. Fishman, D. Berko, J. Engberg, and G. Gross Chimeric {beta}2 microglobulin/CD3{zeta} polypeptides expressed in T cells convert MHC class I peptide ligands into T cell activation receptors: a potential tool for specific targeting of pathogenic CD8+ T cells Int. Immunol., November 1, 2003; 15(11): 1379 - 1387. [Abstract] [Full Text] [PDF]
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H. Shao, S. Lei, S. L. Sun, J. Xiang, H. J. Kaplan, and D. Sun CpG-Containing Oligodeoxynucleotide 1826 Converts the Weak Uveitogenic Rat Interphotoreceptor Retinoid-Binding Protein Peptide 1181-1191 into a Strong Uveitogen J. Immunol., November 1, 2003; 171(9): 4780 - 4785. [Abstract] [Full Text] [PDF]
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M. Schroeter, G. Stoll, R. Weissert, H.-P. Hartung, H. Lassmann, and S. Jander CD8+ Phagocyte Recruitment in Rat Experimental Autoimmune Encephalomyelitis: Association with Inflammatory Tissue Destruction Am. J. Pathol., October 1, 2003; 163(4): 1517 - 1524. [Abstract] [Full Text] [PDF]
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L. Battistini, L. Piccio, B. Rossi, S. Bach, S. Galgani, C. Gasperini, L. Ottoboni, D. Ciabini, M. D. Caramia, G. Bernardi, et al. CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1 Blood, June 15, 2003; 101(12): 4775 - 4782. [Abstract] [Full Text] [PDF]
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M. Khare, M. Rodriguez, and C. S. David HLA class II transgenic mice authenticate restriction of myelin oligodendrocyte glycoprotein-specific immune response implicated in multiple sclerosis pathogenesis Int. Immunol., April 1, 2003; 15(4): 535 - 546. [Abstract] [Full Text] [PDF]
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M. Djerbi, K.-B. Abdul-Majid, M. Abedi-Valugerdi, T. Olsson, R. A. Harris, and A. Grandien Expression of the Long Form of Human FLIP by Retroviral Gene Transfer of Hemopoietic Stem Cells Exacerbates Experimental Autoimmune Encephalomyelitis J. Immunol., February 15, 2003; 170(4): 2064 - 2073. [Abstract] [Full Text] [PDF]
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D. Sun, Y. Zhang, B. Wei, S. C. Peiper, H. Shao, and H. J. Kaplan Encephalitogenic activity of truncated myelin oligodendrocyte glycoprotein (MOG) peptides and their recognition by CD8+ MOG-specific T cells on oligomeric MHC class I molecules Int. Immunol., February 1, 2003; 15(2): 261 - 268. [Abstract] [Full Text] [PDF]
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O. Stuve, S. Youssef, A. J. Slavin, C. L. King, J. C. Patarroyo, D. L. Hirschberg, W. J. Brickey, J. M. Soos, J. F. Piskurich, H. A. Chapman, et al. The Role of the MHC Class II Transactivator in Class II Expression and Antigen Presentation by Astrocytes and in Susceptibility to Central Nervous System Autoimmune Disease J. Immunol., December 15, 2002; 169(12): 6720 - 6732. [Abstract] [Full Text] [PDF]
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K. Nicolson, S. Freland, C. Weir, B. Delahunt, R. A. Flavell, and B. T. Backstrom Induction of experimental autoimmune encephalomyelitis in the absence of c-Jun N-terminal kinase 2 Int. Immunol., August 1, 2002; 14(8): 849 - 856. [Abstract] [Full Text] [PDF]
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V. Taneja, N. Taneja, T. Paisansinsup, M. Behrens, M. Griffiths, H. Luthra, and C. S. David CD4 and CD8 T Cells in Susceptibility/Protection to Collagen-Induced Arthritis in HLA-DQ8-Transgenic Mice: Implications for Rheumatoid Arthritis J. Immunol., June 1, 2002; 168(11): 5867 - 5875. [Abstract] [Full Text] [PDF]
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T. F. Meehan and H. F. DeLuca CD8+ T cells are not necessary for 1alpha ,25-dihydroxyvitamin D3 to suppress experimental autoimmune encephalomyelitis in mice PNAS, April 16, 2002; 99(8): 5557 - 5560. [Abstract] [Full Text] [PDF]
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S. M. Tompkins, J. Padilla, M. C. Dal Canto, J. P.-Y. Ting, L. Van Kaer, and S. D. Miller De Novo Central Nervous System Processing of Myelin Antigen Is Required for the Initiation of Experimental Autoimmune Encephalomyelitis J. Immunol., April 15, 2002; 168(8): 4173 - 4183. [Abstract] [Full Text] [PDF]
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C. Du and S. Sriram Increased Severity of Experimental Allergic Encephalomyelitis in lyn-/- Mice in the Absence of Elevated Proinflammatory Cytokine Response in the Central Nervous System J. Immunol., March 15, 2002; 168(6): 3105 - 3112. [Abstract] [Full Text] [PDF]
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M. Jacobsen, S. Cepok, E. Quak, M. Happel, R. Gaber, A. Ziegler, S. Schock, W. H. Oertel, N. Sommer, and B. Hemmer Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients Brain, March 1, 2002; 125(3): 538 - 550. [Abstract] [Full Text] [PDF]
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L. Pewe and S. Perlman Cutting Edge: CD8 T Cell-Mediated Demyelination Is IFN-{gamma} Dependent in Mice Infected with a Neurotropic Coronavirus J. Immunol., February 15, 2002; 168(4): 1547 - 1551. [Abstract] [Full Text] [PDF]
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L. Steinman Gene microarrays and experimental demyelinating disease: a tool to enhance serendipity Brain, October 1, 2001; 124(10): 1897 - 1899. [Full Text] [PDF]
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 L. Steinman Myelin-Specific Cd8 T Cells in the Pathogenesis of Experimental Allergic Encephalitis and Multiple Sclerosis J. Exp. Med., September 3, 2001; 194(5): f27 - f30. [Full Text] [PDF]
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T. F. Meehan and H. F. DeLuca CD8+ T cells are not necessary for 1alpha ,25-dihydroxyvitamin D3 to suppress experimental autoimmune encephalomyelitis in mice PNAS, April 16, 2002; 99(8): 5557 - 5560. [Abstract] [Full Text] [PDF]
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