Regulatory T cell suppression is potentiated by target T cells in a cell contact, IL-35- and IL-10-dependent manner

J Immunol. 2009 May 15;182(10):6121-8. doi: 10.4049/jimmunol.0803646.

Abstract

Regulatory T cells (T(reg)) are believed to suppress conventional T cell (T(conv)) proliferation in vitro in a contact-dependent, cytokine-independent manner, based in part on experiments in which T(reg) and T(conv) are separated by a permeable membrane. We show that the production of IL-35, a novel inhibitory cytokine expressed by natural T(reg), increases substantially following contact with T(conv). Surprisingly, T(reg) were able to mediate potent suppression of T(conv) across a permeable membrane when placed in direct contact with T(conv) in the upper chamber of a Transwell plate. Suppression was IL-35 and IL-10 dependent, and T(conv) activation was required for maximal potentiation of T(reg) suppression. These data suggest that it is the induction of suppression, rather than the function of T(reg) that is obligatorily contact dependent.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Communication / immunology*
  • Cell Proliferation
  • Flow Cytometry
  • Immunoprecipitation
  • Interleukin-10 / immunology*
  • Interleukins / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Knockout
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Interleukins
  • Interleukin-10