IFN-gamma receptor signaling regulates memory CD8+ T cell differentiation

J Immunol. 2010 Mar 15;184(6):2855-62. doi: 10.4049/jimmunol.0902708. Epub 2010 Feb 17.

Abstract

IFN-gamma regulates multiple processes in the immune system. Although its antimicrobial effector functions are well described, less is known about the mechanisms by which IFN-gamma regulates CD8(+) T cell homeostasis. With the help of adoptive T cell transfers, we show in this study that IFN-gammaR signaling in CD8(+) T cells is dispensable for expansion, contraction, and memory differentiation in response to peptide vaccination. In contrast, host IFN-gammaR signaling counterregulates CD8(+) T cell responses and the generation of effector memory T cell processes, which are partially regulated by CD11b(+) cells. Similar to vaccination-induced proliferation, host IFN-gammaR signaling limits the expansion of naive CD8(+) T cells and their differentiation into effector memory-like T cells in lymphopenic mice. In contrast to peptide vaccination, IFN-gammaR signaling in CD8(+) T cells contributes to memory fate decision in response to lymphopenia, an effect that is fully reversed by high-affinity TCR ligands. In conclusion, we show that host IFN-gammaR signaling controls the magnitude of CD8(+) T cell responses and subsequent memory differentiation under lymphopenic and nonlymphopenic conditions. In contrast, IFN-gammaR signaling in CD8(+) T cells does not affect cell numbers under either condition, but it directs memory fate decision in response to weak TCR ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / transplantation
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Chickens
  • Coculture Techniques
  • Immunization
  • Immunologic Memory*
  • Interferon gamma Receptor
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Ligands
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / immunology
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Receptors, Interferon / deficiency
  • Receptors, Interferon / genetics
  • Receptors, Interferon / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / immunology*

Substances

  • Ligands
  • Lipopolysaccharides
  • OVA-8
  • Peptide Fragments
  • Receptors, Interferon
  • Interferon-gamma
  • Ovalbumin