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

Abstract

The interleukin 2 (IL-2) receptor βc chain (IL-2Rβc) is known to regulate the development and function of distinct lymphocyte populations. Thus far, the functions of the IL-2Rβc cytoplasmic subregions have been studied extensively by using cultured cell lines; however, this approach has limitations with respect to their functions in distinct primary lymphocyte populations. In the present study, we generated mice each expressing a mutant form of an IL-2Rβc transgene, lacking the cytoplasmic A- or H-region, on an IL-2Rβc null background. We show that lack of the H-region, which mediates activation of the Stat5/Stat3 transcription factors, selectively affects the development of natural killer cells and T cells bearing the γδ T cell receptor. This region is also required for the IL-2-induced proliferation of T cells in vitro, by upregulating IL-2Rα expression. In contrast, the A-region, which mediates activation of the Src family protein tyrosine kinase (PTK) members, contributes to downregulation of the T cell proliferation function. The IL-2Rβc null mutant mice develop severe autoimmune symptoms; these are all suppressed following the expression of either of the mutants, suggesting that neither the Stats nor the Src PTK members are required. Thus, our present approach offers new insights into the functions of these cytoplasmic subregions of the IL-2Rβc chain.