Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures

Nature. 1989 Jan 12;337(6203):181-4. doi: 10.1038/337181a0.

Abstract

The receptors found on most T lymphocytes bind to antigen presented on major histocompatibility complex proteins and consist of dimers of alpha- and beta-polypeptides associated with the invariant CD3 complex. A fully competent immune system requires a diverse array of T-cell antigen receptors (TCRs) with different specificities. This diversity is generated by rearrangement of TCR alpha- and beta-chain gene segments within the thymus where the receptors are first expressed. Any cells carrying self-reactive receptors must be eliminated, suppressed or inactivated so that destructive autoimmunity is avoided. Recently, compelling evidence has shown that one process involved in producing such self-tolerance is clonal deletion of autoreactive cells within the thymus by an as-yet-undefined mechanism. Here we show that engaging the CD3/TCR complex of immature mouse thymocytes with anti-CD3 antibodies produces DNA degradation and cell death through the endogenous pathway of apoptosis. Activation of this process in immature T cells by the binding of the TCR to self-antigens may therefore be the mechanism which produces clonal deletion and consequently self-tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies*
  • Antigen-Antibody Complex
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD3 Complex
  • Cell Survival
  • Cells, Cultured
  • Mice
  • Organ Culture Techniques
  • Receptors, Antigen, T-Cell / immunology*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Antibodies
  • Antigen-Antibody Complex
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • Receptors, Antigen, T-Cell