{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:45:36Z","timestamp":1791287136328,"version":"4.1.0"},"reference-count":49,"publisher":"American Diabetes Association","issue":"10","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,10,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Transforming growth factor-\u03b2 (TGF-\u03b2) can exhibit strong immune suppression but has also been shown to promote T-cell growth. We investigated the differential effect of this cytokine on CD8+ T-cells in autoimmunity and antiviral immunity.<\/jats:p>\n                  <jats:p>RESEARCH DESIGN AND METHODS\u2014We used mouse models for virally induced type 1 diabetes in conjunction with transgenic systems enabling manipulation of TGF-\u03b2 expression or signaling in vivo.<\/jats:p>\n                  <jats:p>RESULTS\u2014Surprisingly, when expressed selectively in the pancreas, TGF-\u03b2 reduced apoptosis of differentiated autoreactive CD8+ T-cells, favoring their expansion and infiltration of the islets. These results pointed to drastically opposite roles of TGF-\u03b2 on nai\u0308ve compared with antigen-experienced\/memory CD8+ T-cells. Indeed, in the absence of functional TGF-\u03b2 signaling in T-cells, fast-onset type 1 diabetes caused by activation of nai\u0308ve CD8+ T-cells occurred faster, whereas slow-onset disease depending on accumulation and activation of antigen-experienced\/memory CD8+ T-cells was decreased. TGF-\u03b2 receptor\u2013deficient CD8+ T-cells showed enhanced activation and expansion after lymphocytic choriomeningitis virus infection in vivo but were more prone to apoptosis once antigen experienced and failed to survive as functional memory cells. In vitro, TGF-\u03b2 suppressed nai\u0308ve CD8+ T-cell activation and \u03b3-interferon production, whereas memory CD8+ T-cells stimulated in the presence of TGF-\u03b2 showed enhanced survival and increased production of interleukin-17 in conjunction with \u03b3-interferon.<\/jats:p>\n                  <jats:p>CONCLUSIONS\u2014The effect of TGF-\u03b2 on CD8+ T-cells is dependent on their differentiation status and activation history. These results highlight a novel aspect of the pleiotropic nature of TGF-\u03b2 and have implications for the design of immune therapies involving this cytokine.<\/jats:p>","DOI":"10.2337\/db08-0609","type":"journal-article","created":{"date-parts":[[2008,8,8]],"date-time":"2008-08-08T21:07:21Z","timestamp":1218229641000},"page":"2684-2692","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":62,"title":["Transforming Growth Factor-\u03b2 Suppresses the Activation of CD8+ T-Cells When Nai\u0308ve but Promotes Their Survival and Function Once Antigen Experienced"],"prefix":"10.2337","volume":"57","author":[{"given":"Christophe M.","family":"Filippi","sequence":"first","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Juedes","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine E.","family":"Oldham","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie","family":"Ling","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Togher","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Peng","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine, New Haven, Connecticut"},{"name":"Howard Hugues Medical Institute, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias G.","family":"von Herrath","sequence":"additional","affiliation":[{"name":"La Jolla Institute for Allergy and Immunology, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031208275443300_R1","doi-asserted-by":"crossref","unstructured":"Gorelik L, Flavell RA: Transforming growth factor-beta in T-cell biology. 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