FUNCTIONAL-RESPONSES AND APOPTOSIS OF CD25 (IL-2R-ALPHA)-DEFICIENT T-CELLS EXPRESSING A TRANSGENIC ANTIGEN RECEPTOR

IL-2 was initially defined as a T lymphocyte growth factor, but recent studies have provided evidence that it may also play a role in regula ting T cell differentiation, apoptosis, and tolerance. To examine the contribution of IL-2 to these processes, we have bred a class II-restr icted TCR transgene into mice deficient in the alpha-chain of the IL-2 R, CD25. We show that in response to Ag, T cells from these mice are u nable to use IL-2 and, as a result, are less efficient at traversing t he cell cycle, and proliferate less than wild-type cells. Furthermore, CD25 -/- T cells exhibit reduced survival in vitro, even in the prese nce of costimulatory signals. IL-4 and IL-15, a cytokine related to IL -2, enhance the survival and Ag-induced proliferation of CD25 -/- T ce lls. Activated CD25 -/- T cells are resistant to Fas-mediated activati on-induced cell death (AICD), and this defect cannot be corrected by o ther cytokines. Therefore, IL-2 plays a unique role in regulating AICD , but has redundant roles in T cell survival and proliferation in vitr o. The failure of AICD observed with CD25 -/- T cells may explain the unexpected observation that deficiency of IL-2 or of the alpha- or bet a-chain of the IL-2R results not in immunodeficiency, but in autoimmun e disease.