Pathogen-specific CD8 T cell responses are directly inhibited by IL-10

J Immunol. 2007 Oct 1;179(7):4520-8. doi: 10.4049/jimmunol.179.7.4520.

Abstract

Regulation of CD8 T cell expansion and contraction is essential for successful immune defense against intracellular pathogens. IL-10 is a regulatory cytokine that can restrict T cell responses by inhibiting APC functions. IL-10, however, can also have direct effects on T cells. Although blockade or genetic deletion of IL-10 enhances T cell-mediated resistance to infections, the extent to which IL-10 limits in vivo APC function or T cell activation/proliferation remains unknown. Herein, we demonstrate that primary and memory CD8 T cell responses following Listeria monocytogenes infection are enhanced by the absence of IL-10. Surface expression of the IL-10R is transiently up-regulated on CD8 T cells following activation, suggesting that activated T cells can respond to IL-10 directly. Consistent with this notion, CD8 T cells lacking IL-10R2 underwent greater expansion than wild-type T cells upon L. monocytogenes infection. The absence of IL-10R2 on APCs, in contrast, did not enhance T cell responses following infection. Our studies demonstrate that IL-10 produced during bacterial infection directly limits expansion of pathogen-specific CD8 T cells and reveal an extrinsic regulatory mechanism that modulates the magnitude of memory T cell responses.

Publication types

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

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Immunologic Memory / immunology
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / immunology*
  • Listeria monocytogenes / immunology*
  • Listeria monocytogenes / pathogenicity*
  • Listeriosis / immunology
  • Listeriosis / metabolism
  • Listeriosis / pathology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Receptors, Interleukin-10 / deficiency
  • Receptors, Interleukin-10 / genetics
  • Receptors, Interleukin-10 / immunology
  • Receptors, Interleukin-10 / metabolism
  • Signal Transduction / immunology

Substances

  • Receptors, Interleukin-10
  • Interleukin-10