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  • Regulation of T cell activation is a crucial component of balanced functioning of the immune system. If the T cell response is too great and activation of self-responsive cells or unstimulated cells is not suppressed, then autoimmune disorders or tissue injury can result. Unstimulated T cells are maintained in a quiescent state and the activity of self-reactive T cells is maintained in an anergic state in which IL-2 expression is repressed. IL-2 is a cytokine with a key role in the activation and proliferation of T cells. The maintenance of T cells in the anergic or unstimulated state may not involve just an absence of activation, but an active repression of IL-2 expression, T cell proliferation, and activation. TGF beta may play a role in suppressing T cell activation. Tob is a member of a family of genes with anti-proliferative properties that represses T cell activation. Tob expression is highest in unstimulated and anergic T cells, and is reduced in activated T cells. Tob interacts with the TGF activated transcription factors SMAD2 and SMAD4, increasing their binding to the IL-2 promoter, and helping to repress IL-2 expression. This role of Tob suggests that interference in Tob\'s function may lead to autoimmune disease. (This definition may be outdated - see the DesignNote.)
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