A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis

Nature. 1997 Oct 16;389(6652):737-42. doi: 10.1038/39614.

Abstract

Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such active suppression. Here we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RB(high) splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Clone Cells
  • Colitis / immunology
  • Colitis / prevention & control*
  • Cytokines / biosynthesis
  • Humans
  • Immune Tolerance
  • Immunosuppression
  • Inflammatory Bowel Diseases / immunology
  • Interleukin-10 / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Ovalbumin / immunology
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / transplantation

Substances

  • Cytokines
  • Interleukin-10
  • Ovalbumin