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

Hodaka Fujii, Kouetsu Ogasawara, Hidefumi Otsuka, Misao Suzuki, Ken Ichi Yamamura, Taeko Yokochi, Tadaaki Miyazaki, Haruhiko Suzuki, Tak W. Mak, Shinsuke Taki, Tadatsugu Taniguchi

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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.

Original languageEnglish
Pages (from-to)6551-6557
Number of pages7
JournalEMBO Journal
Volume17
Issue number22
Publication statusPublished - 1998 Nov 16

Keywords

  • Interleukin-2 receptor βc chain
  • Lymphocyte development
  • Natural killer cells
  • T cell growth
  • γδ T cells

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Fujii, H., Ogasawara, K., Otsuka, H., Suzuki, M., Yamamura, K. I., Yokochi, T., Miyazaki, T., Suzuki, H., Mak, T. W., Taki, S., & Taniguchi, T. (1998). Functional dissection of the cytoplasmic subregions of the IL-2 receptor βc chain in primary lymphocyte populations. EMBO Journal, 17(22), 6551-6557.