The interleukin-2 receptor γ chain: Its role in the multiple cytokine receptor complexes and T cell development in XSCID

Kazuo Sugamura, Hironobu Asao, Motonari Kondo, Nobuyuki Tanaka, Naoto Ishii, Kazuyuki Ohbo, Masataka Nakamura, Toshikazu Takeshita

Research output: Contribution to journalReview articlepeer-review

334 Citations (Scopus)

Abstract

Interleukin 2 (IL-2), a T cell-derived cytokine, targets a variety of cells to induce their growth, differentiation, and functional activation. IL- 2 inserts signals into the cells through IL-2 receptors expressed on cell surfaces to induce such actions. In humans, the functional IL-2 receptor consists of the subunit complexes of the α, β, and γ chains, or the β and γ chains. The third component, the γ chain, of IL-2 receptor plays a pivotal role in formation of the full-fledged IL-2 receptor; together with the β chain, the γ chain participates in increasing the IL-2 binding affinity and intracellular signal transduction. Moreover, the cytokine receptors for at least IL-2, IL-4, IL-7, IL-9, and IL-15 utilize the same γ chain as an essential subunit. Interestingly, mutations of the γ chain gene cause human X-linked severe combined immunodeficiency (XSCID) characterized by a complete or profound T cell defect. Among the cytokines sharing the γ chain, at least IL-7 is essentially involved in early T cell development in the mouse organ culture system. The molecular identification of the γ chain brought a grasp of the structures and functions of the cytokine receptor and an in-depth understanding of the cause of human XSCID. To investigate the mechanism of XSCID and development of gene therapy for XSCID, knockout mice for the γ chain gene were produced that showed similar but not exactly the same phenotypes as human XSCID.

Original languageEnglish
Pages (from-to)179-205
Number of pages27
JournalAnnual Review of Immunology
Volume14
DOIs
Publication statusPublished - 1996

Keywords

  • T cell development
  • XSCID
  • cytokine receptor
  • interleukin 2
  • signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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