IL-10 directly suppresses CD4 but not CD8 T cell effector and memory responses following acute viral infection

Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3018-23. doi: 10.1073/pnas.0914500107. Epub 2010 Jan 26.

Abstract

Mounting effective T cell responses is critical for eliciting long-lasting immunity following viral infection and vaccination. A multitude of inhibitory and stimulatory factors are induced following infection, and it is the compilation of these signals that quantitatively and qualitatively program the ensuing effector and memory T cell response. In response to lymphocytic choriomeningitis virus (LCMV) infection, the immunosuppressive cytokine IL-10 is rapidly up-regulated; however, how IL-10 is regulating what is often considered an "optimal" immune response is unclear. We demonstrate that IL-10 directly inhibits effector and memory CD4 T cell responses following an acutely resolved viral infection. Blockade of IL-10 enhanced the magnitude and the functional capacity of effector CD4 T cells that translated into increased and more effective memory responses. On the other hand, lack of IL-10 signaling did not impact memory CD8 T cell development. We propose that blockade of IL-10 may be an effective adjuvant to specifically enhance CD4 T cell immunity and protection following vaccination.

Publication types

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

MeSH terms

  • Animals
  • Arenaviridae Infections / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation / immunology*
  • Immunologic Memory / immunology*
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Statistics, Nonparametric

Substances

  • Cytokines
  • Interleukin-10