Cell-intrinsic IL-27 and gp130 cytokine receptor signaling regulates virus-specific CD4⁺ T cell responses and viral control during chronic infection

Immunity. 2013 Sep 19;39(3):548-59. doi: 10.1016/j.immuni.2013.08.010. Epub 2013 Aug 29.

Abstract

The outcome of chronic viral infections, which affect millions of people worldwide, is greatly dependent on CD4⁺ T cells. Here we showed that T cell-specific ablation of the common interleukin-6 (IL-6) family receptor, gp130, profoundly compromised virus-specific CD4⁺ T cell survival, T follicular helper responses, and IL-21 production at late stages of chronic lymphocytic choriomeningitis virus (LCMV) infection. These effects were cell intrinsic for CD4⁺ T cells and were accompanied by a reduction of CD8⁺ T cells, antibodies, and a severe failure in viral control. We identified IL-27 as a gp130 cytokine that promoted antiviral CD4⁺ T cell accumulation in vivo and that rapidly induced IL-21 ex vivo. Furthermore, IL-27R was critical for control of persistent LCMV in vivo. These results reveal that gp130 cytokines (particularly IL-27) are key regulators of CD4⁺ T cell responses during an established chronic viral infection, empowering both humoral and cytotoxic immunity.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Survival
  • Cytokine Receptor gp130 / metabolism*
  • Interleukin-27 / metabolism*
  • Interleukins / biosynthesis
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism*
  • Receptors, Interleukin
  • Receptors, Interleukin-6

Substances

  • Il27ra protein, mouse
  • Interleukin-27
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130
  • interleukin-21