Role of direct effects of IFN-gamma on T cells in the regulation of CD8 T cell homeostasis

J Immunol. 2007 Aug 15;179(4):2115-25. doi: 10.4049/jimmunol.179.4.2115.

Abstract

It is well recognized that IFN-gamma plays a critical role in the control of CD8 T cell expansion and contraction during immune responses to several intracellular pathogens. However, our understanding of the mechanisms underlying the regulation of T cell fate by IFN-gamma is sorely incomplete. Specifically, it is unclear whether regulation of CD8 T cell homeostasis occurs by a T cell intrinsic IFN-gamma pathway. In this study, we have determined the role of the direct effects of IFN-gamma on T cells in regulating the expansion, contraction, and memory phases of the polyclonal CD8 T cell response to an acute viral infection. Using two complementary approaches we demonstrate that the direct effects of IFN-gamma suppress IL-7R expression on Ag-specific effector CD8 T cells, but clonal expansion or deletion of activated CD8 T cells in vivo can occur in the apparent absence of IFN-gammaR signaling in T cells. These findings have clarified fundamental features of control of T cell homeostasis by IFN-gamma in the context of CD8 T cell memory and protective immunity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Animals
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Immunologic Memory / genetics
  • Immunologic Memory / immunology*
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology*
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Knockout
  • Receptors, Interleukin-7 / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology

Substances

  • Antigens, Viral
  • Receptors, Interleukin-7
  • Interferon-gamma