T cell-intrinsic role of IL-6 signaling in primary and memory responses

Elife. 2014 May 19;3:e01949. doi: 10.7554/eLife.01949.

Abstract

Innate immune recognition is critical for the induction of adaptive immune responses; however the underlying mechanisms remain incompletely understood. In this study, we demonstrate that T cell-specific deletion of the IL-6 receptor α chain (IL-6Rα) results in impaired Th1 and Th17 T cell responses in vivo, and a defect in Tfh function. Depletion of Tregs in these mice rescued the Th1 but not the Th17 response. Our data suggest that IL-6 signaling in effector T cells is required to overcome Treg-mediated suppression in vivo. We show that IL-6 cooperates with IL-1β to block the suppressive effect of Tregs on CD4(+) T cells, at least in part by controlling their responsiveness to IL-2. In addition, although IL-6Rα-deficient T cells mount normal primary Th1 responses in the absence of Tregs, they fail to mature into functional memory cells, demonstrating a key role for IL-6 in CD4(+) T cell memory formation.DOI: http://dx.doi.org/10.7554/eLife.01949.001.

Keywords: T cells; cytokines; memory; regulatory T cells.

Publication types

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

MeSH terms

  • Adaptive Immunity* / drug effects
  • Animals
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cells, Cultured
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Immunity, Innate* / drug effects
  • Immunization
  • Immunologic Memory* / drug effects
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Interleukin-6 / pharmacology
  • Interleukin-6 Receptor alpha Subunit / deficiency
  • Interleukin-6 Receptor alpha Subunit / genetics
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Recombinant Proteins / pharmacology
  • Signal Transduction* / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-6 Receptor alpha Subunit
  • Recombinant Proteins
  • Ovalbumin