An IFN-gamma-dependent pathway controls stimulation of memory phenotype CD8+ T cell turnover in vivo by IL-12, IL-18, and IFN-gamma

J Immunol. 2001 May 15;166(10):6007-11. doi: 10.4049/jimmunol.166.10.6007.

Abstract

Unlike naive T cells, memory phenotype (CD44(high)) T cells exhibit a high background rate of turnover in vivo. Previous studies showed that the turnover of memory phenotype CD8(+) (but not CD4(+)) cells in vivo can be considerably enhanced by products of infectious agents such as LPS. Such stimulation is TCR independent and hinges on the release of type I IFNs (IFN-I) which leads to the production of an effector cytokine, probably IL-15. In this study, we describe a second pathway of CD44(high) CD8(+) stimulation in vivo. This pathway is IFN-gamma rather than IFN-I dependent and is mediated by at least three cytokines, IL-12, IL-18, and IFN-gamma. As for IFN-I, these three cytokines are nonstimulatory for purified T cells and under in vivo conditions probably act via production of IL-15.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Division / genetics
  • Cell Division / immunology
  • Cells, Cultured
  • Immunologic Memory* / genetics
  • Immunophenotyping
  • Injections, Intravenous
  • Interferon Type I / metabolism
  • Interferon Type I / physiology
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology*
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / physiology*
  • Interleukin-18 / physiology*
  • Lymphocyte Activation* / genetics
  • Membrane Proteins
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Interferon alpha-beta
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / genetics
  • Recombinant Proteins / administration & dosage
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*

Substances

  • Interferon Type I
  • Interleukin-18
  • Membrane Proteins
  • Receptors, Interferon
  • Recombinant Proteins
  • Receptor, Interferon alpha-beta
  • Interleukin-12
  • Interferon-gamma