Enhancement of CD3-mediated thymocyte apoptosis by the cross-linkage of heat-stable antigen

Immunology. 1996 Oct;89(2):200-4. doi: 10.1046/j.1365-2567.1996.d01-741.x.

Abstract

Heat-stable antigen (HSA) is a murine differentiating antigen that is expressed on both CD4-CD8- double-negative and CD4+CD8+ double-positive thymocytes but not CD4+ or CD8+ single-positive thymocytes. Effects of anti-HSA monoclonal antibody, R13, on thymocyte apoptosis induced by various stimulations were investigated by a single-cell suspension culture system. Immobilized R13 enhanced the CD3-mediated DNA fragmentation and killing of thymocytes but not the dexamethasone-induced or phorbol myristate acetate-induced killing of thymocytes. Immobilized R13 by itself could not induce thymocyte apoptosis. Soluble R13 enhanced CD3-mediated apoptosis when HSA and T-cell receptor (TCR)/CD3 were co-cross-linked by a cross-reactive secondary antibody. Even without the cross-reactive secondary antibody, soluble R13 enhanced CD3-mediated apoptosis, although a greater than 100-fold increase in the amount of R13 was needed to give a similar enhancement compared with immobilized R13. Neither R13 by itself nor R13 plus secondary antibody induced cytosolic calcium influx, whereas R13 enhanced CD3-mediated cytosolic calcium increase. These results suggest a functional role of HSA in promoting the activation-induced apoptosis of thymocytes and the involvement of HSA in negative selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD*
  • Antigens, Differentiation / immunology*
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • CD24 Antigen
  • CD3 Complex / immunology
  • Calcium / metabolism
  • Cells, Cultured
  • Cytosol / metabolism
  • Glucocorticoids / pharmacology
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • CD24 Antigen
  • CD3 Complex
  • Cd24a protein, mouse
  • Glucocorticoids
  • Membrane Glycoproteins
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Tetradecanoylphorbol Acetate
  • Calcium