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Differential requirement of the cytoplasmic subregions of gamma c chain in T cell development and function

S Tsujino1, J P Di Santo, A Takaoka

  • 1Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.

Proceedings of the National Academy of Sciences of the United States of America
|August 30, 2000
PubMed

Insights

The common cytokine receptor gamma chain (gammac) membrane-proximal region is crucial for T cell development in vivo, independent of Janus kinase 3 (Jak3) signaling. This region

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • The common cytokine receptor gamma chain (gammac) is vital for lymphocyte development and function.
  • Its cytoplasmic domain interacts with Janus kinase 3 (Jak3), essential for signaling.
  • The role of the membrane-proximal region of gammac in vivo was previously unknown.

Purpose of the Study:

  • To investigate the in vivo function of the membrane-proximal region of gammac.
  • To determine the role of Jak3-independent signaling pathways mediated by gammac.
  • To elucidate the differential requirements of gammac subregions in T cell biology.

Main Methods:

  • Expression of mutant gammac forms in gammac null mice.
  • Analysis of T lymphopoiesis and Bcl-2 expression in vivo.
  • Assessment of in vitro T cell function.

Main Results:

  • Expression of a mutant gammac lacking the Jak3-binding region restored T lymphopoiesis in vivo.
  • This restoration was associated with increased Bcl-2 expression.
  • T cells restored in vivo exhibited impaired in vitro functions.

Conclusions:

  • The membrane-proximal region of gammac plays a critical, Jak3-independent role in T cell development in vivo.
  • Different cytoplasmic subregions of gammac have distinct roles in T cell development versus function.
  • These findings reveal novel insights into gammac signaling and lymphocyte homeostasis.

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