CD28-mediated Signalling Co-Stimulates Murine T Cells and Prevents Induction of Anergy in T-cell Clones

Nature. 1992 Apr 16;356(6370):607-9. doi: 10.1038/356607a0.

Abstract

Occupancy of the T-cell antigen receptor is insufficient to induce T-cell activation optimally; a second co-stimulatory signal is required. Exposure of T-cell clones to complexes of antigen with major histocompatibility complex molecules in the absence of the co-stimulatory signal induces a state of clonal anergy. This requirement for two stimuli for T-cell activation could have an important role in vivo in establishing peripheral tolerance to antigens not encountered in the thymus. The receptor on T cells required for the co-stimulatory stimulus involved in the prevention of anergy has not been identified. The human T-cell antigen CD28 provides a signal that can synergize with T-cell antigen receptor stimulation in activating T cells to proliferate and secrete lymphokines. Here we report that a monoclonal antibody against the murine homologue of CD28 (ref. 7; J.A.G. et al., manuscript in preparation) can provide a co-stimulatory signal to naive CD4+ T cells and to T-cell clones. Moreover, we demonstrate that this co-stimulatory signal can block the induction of anergy in T-cell clones.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • CD28 Antigens
  • CD4 Antigens / immunology
  • Cells, Cultured
  • DNA Replication
  • Lymphocyte Activation*
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred BALB C
  • Signal Transduction / immunology*
  • Spleen / immunology
  • Spleen / radiation effects
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD4 Antigens