gamma(c) cytokines provide multiple homeostatic signals to naive CD4(+) T cells

Eur J Immunol. 2007 Sep;37(9):2606-16. doi: 10.1002/eji.200737234.


Cytokines signaling through receptors sharing the common gamma chain (gamma(c)), including IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, are critical for the generation and peripheral homeostasis of B, T and NK cells. To identify unique or redundant roles for gamma(c) cytokines in naive CD4(+) T cells, we compared monoclonal populations of CD4(+) T cells from TCR-Tg mice that were gamma(c) (+), gamma(c) (-), CD127(-/-) or CD122(-/-). We found that gamma(c) (-) naive CD4(+) T cells failed to accumulate in the peripheral lymphoid organs and the few remaining cells were characterized by small size, decreased expression of MHC class I and enhanced apoptosis. By over-expressing human Bcl-2, peripheral naive CD4(+) T cells that lack gamma(c) could be rescued. Bcl-2(+) gamma(c) (-) CD4(+) T cells demonstrated enhanced survival characteristics in vivo and in vitro, and could proliferate normally in vitro in response to antigen. Nevertheless, Bcl-2(+) gamma(c) (-) CD4(+) T cells remained small in size, and this phenotype was not corrected by enforced expression of an activated protein kinase B. We conclude that gamma(c) cytokines (primarily but not exclusively IL-7) provide Bcl-2-dependent as well as Bcl-2-independent signals to maintain the phenotype and homeostasis of the peripheral naive CD4(+) T cell pool.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Proliferation
  • Cell Size
  • Cytokines / immunology*
  • Cytokines / metabolism*
  • Enzyme Activation
  • Gene Expression Regulation
  • Homeostasis / immunology*
  • Immunity, Innate / immunology*
  • Interleukin-2 Receptor beta Subunit / metabolism
  • Interleukin-7 Receptor alpha Subunit / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / immunology*


  • Cytokines
  • Interleukin-2 Receptor beta Subunit
  • Interleukin-7 Receptor alpha Subunit
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-akt