CD8(+) T cells sabotage their own memory potential through IFN-γ-dependent modification of the IL-12/IL-15 receptor α axis on dendritic cells

J Immunol. 2012 Apr 15;188(8):3639-47. doi: 10.4049/jimmunol.1101580. Epub 2012 Mar 19.

Abstract

CD8(+) T cell responses have been shown to be regulated by dendritic cells (DCs) and CD4(+) T cells, leading to the tenet that CD8(+) T cells play a passive role in their own differentiation. In contrast, by using a DNA vaccination model, to separate the events of vaccination from those of CD8(+) T cell priming, we demonstrate that CD8(+) T cells, themselves, actively limit their own memory potential through CD8(+) T cell-derived IFN-γ-dependent modification of the IL-12/IL-15Rα axis on DCs. Such CD8(+) T cell-driven cytokine alterations result in increased T-bet and decreased Bcl-2 expression, and thus decreased memory progenitor formation. These results identify an unrecognized role for CD8(+) T cells in the regulation of their own effector differentiation fate and a previously uncharacterized relationship between the balance of inflammation and memory formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Gene Expression Regulation / immunology
  • Humans
  • Immunologic Memory*
  • Interferon-gamma
  • Interleukin-12 / genetics
  • Interleukin-12 / immunology
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • Lymphocyte Activation
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-12 / genetics
  • Receptors, Interleukin-12 / immunology*
  • Receptors, Interleukin-15 / genetics
  • Receptors, Interleukin-15 / immunology*
  • Signal Transduction / immunology
  • Vaccination
  • Vaccines, DNA / immunology

Substances

  • Interleukin-15
  • Receptors, Interleukin-12
  • Receptors, Interleukin-15
  • Vaccines, DNA
  • Interleukin-12
  • Interferon-gamma