T lymphocyte-mediated control of autoimmunity

Novartis Found Symp. 1998;215:200-11; discussion 211-30. doi: 10.1002/9780470515525.ch15.

Abstract

Autoreactive T cells can be readily identified in the peripheral lymphocyte pool of both humans and experimental animals. Peripheral tolerance may be maintained by regulatory/suppressor T cells which prevent the activation of autoantigen-specific cells. Mice thymectomized on day 3 of life (d3Tx) develop a wide spectrum of organ-specific autoimmune diseases. Reconstitution of d3Tx mice with CD4+ CD25+ T cells from normal mice prevents the development of disease. Similarly, CD4+ CD25+ T cells prevent the transfer of disease by autoantigen-specific cloned T cells derived from d3Tx mice. Thus, regulatory T cells can prevent both the induction and effector function of autoreactive T cells. In vitro, the CD4+ CD25+ population is anergic to stimulation through the T cell receptor (TCR) and suppresses the proliferative responses of normal CD4+ CD25- cells by a contract-dependent mechanism. Suppression is not MHC-dependent, but requires activation of the CD4+ CD25+ population. The mechanism of suppression in vivo and the target antigen(s) of this unique regulatory population remain to be characterized.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoimmune Diseases / etiology
  • Autoimmunity*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Lineage
  • Clonal Anergy
  • Immune Tolerance*
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-2 / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Thymectomy

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2