Regulatory mechanism of homeostatic T cell proliferation

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Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) transduces inhibitory signals for T cell activation and regulates T cell homeostasis in vivo. Indeed, mice deficient for CTLA-4 exhibit lymphoproliferative autoimmune disease and early death at 3-4 wk of age. We show that T cells activated in the absence of IL-2/IL-2R interaction fail to express CTLA-4 on the cell surface. The lack of surface expression is due to impaired mRNA expression but not to a defect in protein trafficking. Our results demonstrate that IL-2 is essential for CTLA-4 induction in activated T cells, and suggest that the impairment of CTLA-4 induction is one of mechanisms causing fatal autoimmune disease observed in mice lacking IL-2/IL-2R system in vivo.