{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:04:23Z","timestamp":1791374663650,"version":"4.3.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2010,5,1]],"date-time":"2010-05-01T00:00:00Z","timestamp":1272672000000},"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":[[2010,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>High titers of autoantibodies against glutamic acid decarboxylase (GAD) 65 are commonly observed in patients suffering from type 1 diabetes as well as stiff-person syndrome (SPS), a disorder that affects the CNS, and a variant of SPS, progressive encephalomyelitis with rigidity and myoclonus. Although there is a considerable amount of data focusing on the role of GAD65-specific CD4+ T cells in type 1 diabetes, little is known about their role in SPS. In this study, we show that mice possessing a monoclonal GAD65-specific CD4+ T cell population (4B5, PA19.9G11, or PA17.9G7) develop a lethal encephalomyelitis-like disease in the absence of any other T cells or B cells. GAD65-reactive CD4+ T cells were found throughout the CNS in direct concordance with GAD65 expression and activated microglia: proximal to the circumventricular organs at the interface between the brain parenchyma and the blood-brain barrier. In the presence of B cells, high titer anti-GAD65 autoantibodies were generated, but these had no effect on the incidence or severity of disease. In addition, GAD65-specific CD4+ T cells isolated from the brain were activated and produced IFN-\u03b3. These findings suggest that GAD65-reactive CD4+ T cells alone mediate a lethal encephalomyelitis-like disease that may serve as a useful model to study GAD65-mediated diseases of the CNS.<\/jats:p>","DOI":"10.4049\/jimmunol.0903728","type":"journal-article","created":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T23:35:48Z","timestamp":1269646548000},"page":"4863-4870","source":"Crossref","is-referenced-by-count":71,"title":["Central Nervous System Destruction Mediated by Glutamic Acid Decarboxylase-Specific CD4+ T Cells"],"prefix":"10.1093","volume":"184","author":[{"given":"Amanda R","family":"Burton","sequence":"first","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Baquet","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S","family":"Eisenbarth","sequence":"additional","affiliation":[{"name":"Barbara Davis Center for Childhood Diabetes, University of Colorado Denver , Aurora, CO 80045"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Tisch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of North Carolina , Chapel Hill, NC 27599"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Smeyne","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology, St. Jude Children\u2019s Research Hospital , Memphis, TN 38105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Creg J","family":"Workman","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario A A","family":"Vignali","sequence":"additional","affiliation":[{"name":"Department of Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,5,1]]},"reference":[{"key":"2025032604261763600_r1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/366069a0","article-title":"Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes.","volume":"366","author":"Kaufman","year":"1993","journal-title":"Nature"},{"key":"2025032604261763600_r2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/366072a0","article-title":"Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice.","volume":"366","author":"Tisch","year":"1993","journal-title":"Nature"},{"key":"2025032604261763600_r3","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1056\/NEJM199005313222202","article-title":"Autoantibodies to GABA-ergic neurons and pancreatic beta cells in stiff-man syndrome.","volume":"322","author":"Solimena","year":"1990","journal-title":"N. 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