Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins

After autoimmune inflammation, interactions between CD95 and its ligand (CD 95L) mediate thyrocyte destruction in Hashimoto's thyroiditis (HT). Convers ely, thyroid autoimmune processes that lead to Graves' disease (GD) result in autoantibody-mediated thyrotropin receptor stimulation without thyrocyte depletion,We found that GD thyrocytes expressed CD95 and CD95L in a simila r manner to HT thyrocytes, but did not undergo CD95-induced apoptosis eithe r in vivo or in vitro. This pattern was due to the differential production of T(H)1 and T(H)2 cytokines. Interferon gamma promoted caspase up-regulati on and CD95-induced apoptosis in HT thyrocytes, whereas interleukin 4 and i nterleukin 10 protected GD thyrocytes by potent up-regulation of cFLIP and Bcl-x(L), which prevented CD95-induced apoptosis in sensitized thyrocytes. Thus, modulation of apoptosis-related proteins by T(H)1 and T(H)2 cytokines controls thyrocyte survival in thyroid autoimmunity.