Transforming Growth Factor-β Suppresses the Activation of CD8+ T-Cells When Naïve but Promotes Their Survival and Function Once Antigen Experienced

• DOI: 10.2337/db08-0609
• Publication Date: 2008-08-09T01:07:21Z
• Authors: Christophe M. Fil...; Amy E. Juedes; Janine E. Oldham; Ellie Ling; Lisa Togher; Yufeng Peng; Richard A. Flavell; Matthias G. von H...
• Keywords: 0301 basic medicine; Mice, Inbred BALB C; Cell Survival; Apoptosis; Autoimmunity; Mice, Transgenic; CD8-Positive T-Lymphocytes; Flow Cytometry; Immunohistochemistry; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Mice, Inbred NOD; Transforming Growth Factor beta; In Situ Nick-End Labeling; Animals; Immunology and Transplantation; Pancreas; Cells, Cultured

Transforming growth factor-beta (TGF-beta) 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.We used mouse models for virally induced type 1 diabetes conjunction with transgenic systems enabling manipulation TGF-beta expression or signaling vivo.Surprisingly, when expressed selectively pancreas, reduced apoptosis differentiated autoreactive T-cells, favoring their expansion infiltration islets. These results pointed drastically opposite roles naïve compared antigen-experienced/memory T-cells. Indeed, absence functional fast-onset caused by activation occurred faster, whereas slow-onset disease depending accumulation was decreased. receptor-deficient showed enhanced after lymphocytic choriomeningitis virus infection vivo were more prone once antigen experienced failed survive as memory cells. In vitro, suppressed gamma-interferon production, stimulated presence survival increased production interleukin-17 gamma-interferon.The is dependent differentiation status history. highlight a novel aspect pleiotropic nature have implications design therapies involving cytokine.