{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:35:03Z","timestamp":1791178503710,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T00:00:00Z","timestamp":1330560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Experimental autoimmune encephalomyelitis (EAE) is a widely used model of multiple sclerosis. In NOD mice, EAE develops as a relapsing\u2013remitting disease that transitions to a chronic progressive disease, making the NOD model the only mouse model that recapitulates the full clinical disease course observed in most multiple sclerosis patients. We have generated a TCR transgenic mouse that expresses the \u03b1- and \u03b2-chains of a myelin oligodendrocyte glycoprotein (MOG) 35\u201355\u2013reactive TCR (1C6) on the NOD background. 1C6 TCR transgenic mice spontaneously generate both CD4+ and CD8+ T cells that recognize MOG and produce proinflammatory cytokines, allowing for the first time to our knowledge the simultaneous examination of myelin-reactive CD4+ and CD8+ T cells in the same host. 1C6 CD8+ T cells alone can induce optic neuritis and mild EAE with delayed onset; however, 1C6 CD4+ T cells alone induce severe EAE and predominate in driving disease when both cell types are present. When 1C6 mice are crossed with mice bearing an IgH specific for MOG, the mice develop spontaneous EAE with high incidence, but surprisingly the disease pattern does not resemble the neuromyelitis optica-like disease observed in mice bearing CD4+ T cells and B cells reactive to MOG on the C57BL\/6 background. Collectively, our data show that although myelin-reactive CD8+ T cells contribute to disease, disease is primarily driven by myelin-reactive CD4+ T cells and that the coexistence of myelin-reactive T and B cells does not necessarily result in a distinct pathological phenotype.<\/jats:p>","DOI":"10.4049\/jimmunol.1102186","type":"journal-article","created":{"date-parts":[[2012,1,27]],"date-time":"2012-01-27T01:29:46Z","timestamp":1327627786000},"page":"2084-2092","source":"Crossref","is-referenced-by-count":65,"title":["A Transgenic Model of Central Nervous System Autoimmunity Mediated by CD4+ and CD8+ T and B Cells"],"prefix":"10.1093","volume":"188","author":[{"given":"Ana C","family":"Anderson","sequence":"first","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rucha","family":"Chandwaskar","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna M","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Solomon","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roselynn","family":"Rodriguez-Manzanet","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Greve","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond A","family":"Sobel","sequence":"additional","affiliation":[{"name":"Palo Alto Veterans Administration Health Care System , Palo Alto, CA 94304"},{"name":"Department of Pathology, Stanford University School of Medicine , Palo Alto, CA 94304"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijay K","family":"Kuchroo","sequence":"additional","affiliation":[{"name":"Center for Neurologic Diseases, Brigham and Women\u2019s Hospital and Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,3,1]]},"reference":[{"key":"2025032409541309500_r1","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/5941","article-title":"QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2","volume":"21","author":"Encinas","year":"1999","journal-title":"Nat. Genet."},{"key":"2025032409541309500_r2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0092-8674(00)81110-1","article-title":"Genetic analysis of autoimmune disease","volume":"85","author":"Vyse","year":"1996","journal-title":"Cell"},{"key":"2025032409541309500_r3","doi-asserted-by":"crossref","first-page":"9979","DOI":"10.1073\/pnas.95.17.9979","article-title":"Clustering of non-major histocompatibility complex susceptibility candidate loci in human autoimmune diseases","volume":"95","author":"Becker","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409541309500_r4","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/0092-8674(93)90074-Z","article-title":"Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity","volume":"72","author":"Goverman","year":"1993","journal-title":"Cell"},{"key":"2025032409541309500_r5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/1074-7613(95)90170-1","article-title":"Low avidity recognition of self-antigen by T cells permits escape from central tolerance","volume":"3","author":"Liu","year":"1995","journal-title":"Immunity"},{"key":"2025032409541309500_r6","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0092-8674(94)90419-7","article-title":"High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice","volume":"78","author":"Lafaille","year":"1994","journal-title":"Cell"},{"key":"2025032409541309500_r7","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1073\/pnas.97.7.3412","article-title":"Fulminant spontaneous autoimmunity of the central nervous system in mice transgenic for the myelin proteolipid protein-specific T cell receptor","volume":"97","author":"Waldner","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409541309500_r8","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1084\/jem.20021603","article-title":"Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis","volume":"197","author":"Bettelli","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025032409541309500_r9","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1084\/jem.192.3.393","article-title":"Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction","volume":"192","author":"Babbe","year":"2000","journal-title":"J. Exp. Med."},{"key":"2025032409541309500_r10","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1093\/brain\/120.8.1461","article-title":"The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion","volume":"120","author":"Gay","year":"1997","journal-title":"Brain"},{"key":"2025032409541309500_r11","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1093\/brain\/awf059","article-title":"Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients","volume":"125","author":"Jacobsen","year":"2002","journal-title":"Brain"},{"key":"2025032409541309500_r12","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.4049\/jimmunol.160.6.3056","article-title":"MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes","volume":"160","author":"Jurewicz","year":"1998","journal-title":"J. Immunol."},{"key":"2025032409541309500_r13","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1084\/jem.194.5.669","article-title":"A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis","volume":"194","author":"Huseby","year":"2001","journal-title":"J. Exp. Med."},{"key":"2025032409541309500_r14","doi-asserted-by":"crossref","first-page":"7579","DOI":"10.4049\/jimmunol.166.12.7579","article-title":"Myelin antigen-specific CD8+ T cells are encephalitogenic and produce severe disease in C57BL\/6 mice","volume":"166","author":"Sun","year":"2001","journal-title":"J. Immunol."},{"key":"2025032409541309500_r15","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1002\/eji.200425660","article-title":"Specificity, magnitude, and kinetics of MOG-specific CD8+ T cell responses during experimental autoimmune encephalomyelitis","volume":"35","author":"Ford","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"2025032409541309500_r16","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0002-9343(48)90389-1","article-title":"Quantitative estimation of the albumin and gamma globulin in normal and pathologic cerebrospinal fluid by immunochemical methods","volume":"4","author":"Kabat","year":"1948","journal-title":"Am. J. Med."},{"key":"2025032409541309500_r17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0165-5728(00)00409-4","article-title":"B cells and antibodies in CNS demyelinating disease","volume":"112","author":"Cross","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"2025032409541309500_r18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1084\/jem.188.1.169","article-title":"B lymphocytes producing demyelinating autoantibodies: development and function in gene-targeted transgenic mice","volume":"188","author":"Litzenburger","year":"1998","journal-title":"J. Exp. Med."},{"key":"2025032409541309500_r19","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1172\/JCI28334","article-title":"Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice","volume":"116","author":"Bettelli","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025032409541309500_r20","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1172\/JCI28330","article-title":"Spontaneous opticospinal encephalomyelitis in a double-transgenic mouse model of autoimmune T cell\/B cell cooperation","volume":"116","author":"Krishnamoorthy","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2025032409541309500_r21","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/0022-1759(95)00002-R","article-title":"Cassette vectors directing expression of T cell receptor genes in transgenic mice","volume":"180","author":"Kouskoff","year":"1995","journal-title":"J. Immunol. Methods"},{"key":"2025032409541309500_r22","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1097\/00005072-199009000-00002","article-title":"Acute experimental allergic encephalomyelitis in SJL\/J mice induced by a synthetic peptide of myelin proteolipid protein","volume":"49","author":"Sobel","year":"1990","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"2025032409541309500_r23","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.256.5060.1210","article-title":"Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-\/- mice","volume":"256","author":"Koh","year":"1992","journal-title":"Science"},{"key":"2025032409541309500_r24","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1126\/science.256.5060.1213","article-title":"Role of CD8+ T cells in murine experimental allergic encephalomyelitis","volume":"256","author":"Jiang","year":"1992","journal-title":"Science"},{"key":"2025032409541309500_r25","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/ni1073","article-title":"CD8+ T cells maintain tolerance to myelin basic protein by \u2018epitope theft\u2019","volume":"5","author":"Perchellet","year":"2004","journal-title":"Nat. Immunol."},{"key":"2025032409541309500_r26","doi-asserted-by":"crossref","first-page":"14040","DOI":"10.1073\/pnas.0804970105","article-title":"Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic protein","volume":"105","author":"Perchellet","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409541309500_r27","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/ni.1888","article-title":"Viral infection triggers central nervous system autoimmunity via activation of CD8+ T cells expressing dual TCRs","volume":"11","author":"Ji","year":"2010","journal-title":"Nat. Immunol."},{"key":"2025032409541309500_r28","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1038\/nm.1881","article-title":"Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis","volume":"14","author":"Friese","year":"2008","journal-title":"Nat. Med."},{"key":"2025032409541309500_r29","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jaut.2010.01.003","article-title":"Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis","volume":"35","author":"York","year":"2010","journal-title":"J. Autoimmun."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/188\/5\/2084\/61632021\/1102186.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/188\/5\/2084\/61632021\/1102186.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T17:55:40Z","timestamp":1743098140000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/188\/5\/2084\/7981363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,1]]},"references-count":29,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,3,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1102186","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,3]]},"published":{"date-parts":[[2012,3,1]]}}}