Functional dissection of the cytoplasmic subregions of the IL-2 receptor beta c chain in primary lymphocyte populations

The interleukin 2 (IL-2) receptor beta c chain (IL-2R beta c) is known to r egulate the development and function of distinct lymphocyte populations. Th us far, the functions of the IL-2R beta c cytoplasmic subregions have been studied extensively by using cultured cell lines; however, this approach ha s limitations with respect to their functions in distinct primary lymphocyt e populations. In the present study, we generated mice each expressing a mu tant form of an IL-2R beta c transgene, lacking the cytoplasmic A- or II-re gion, on an IL-2R beta c null background, We show that lack of the II-regio n, which mediates activation of the Stat5/Stat3 transcription factors, sele ctively affects the development of natural killer cells and T cells bearing the gamma delta T cell receptor. This region is also required for the IL-2 -induced proliferation of T cells in vitro, by upregulating IL-2R alpha exp ression. In contrast, the A-region, which mediates activation of the Src fa mily protein tyrosine kinase (PTK) members, contributes to downregulation o f the T cell proliferation function. The IL-2R beta c null mutant mice deve lop severe autoimmune symptoms; these are all suppressed following the expr ession of either of the mutants, suggesting that neither the Stats nor the Src PTK members are required. Thus, our present approach offers new insight s into the functions of these cytoplasmic subregions of the IL-2R beta c ch ain.