CD9-mediated costimulation of TCR-triggered naive T cells leads to activation followed by apoptosis

J Immunol. 1997 Oct 15;159(8):3799-807.


The induction of full activation or death in TCR-triggered T cells depends largely on whether appropriate costimulatory signals are provided. In this study, we show that the costimulation of CD9 on naive T cells during TCR stimulation results in transient, albeit potent, activation followed by apoptosis, rather than full activation. Anti-CD9 mAb synergized with suboptimal doses of anti-CD3 mAb in inducing T cell activation. [3H]TdR incorporation determined 2 days after CD9 costimulation was as potent as that induced by CD28 costimulation. In contrast to progressive T cell proliferation induced by CD28 costimulation, CD9 costimulation led to the induction of apoptosis of once-activated T cells. Although IL-2R expression was induced significantly earlier and to a greater degree after CD9 costimulation than after CD28 costimulation, CD9 costimulation only transiently produced a small amount of IL-2 and induced apparently low levels of bcl-xL compared with those observed in CD28 costimulation. Addition of rIL-2 to cultures of CD9 costimulation induced strikingly enhanced expression of bcl proteins, especially of bcl-xL, and protected TCR-stimulated T cells from apoptosis. These data indicate that CD9-mediated costimulation of TCR-triggered naive T cells leads to activation followed by apoptosis as the result of failure to generate a positive signal for sufficient levels of IL-2 production.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / physiology
  • Animals
  • Antigens, CD / physiology*
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Cell Division / drug effects
  • Cell Division / immunology
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation* / drug effects
  • Membrane Glycoproteins*
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / drug effects
  • Receptors, Antigen, T-Cell / physiology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tetraspanin 29
  • bcl-X Protein


  • Adjuvants, Immunologic
  • Antigens, CD
  • Bcl2l1 protein, mouse
  • Cd9 protein, mouse
  • Interleukin-2
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • Tetraspanin 29
  • bcl-X Protein