The Journal of Immunology, Vol 159, Issue 8 3799-3807, Copyright © 1997 by American Association of Immunologists

ARTICLES

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

XG Tai, K Toyooka, Y Yashiro, R Abe, CS Park, T Hamaoka, M Kobayashi, S Neben and H Fujiwara
Biomedical Research Center, Osaka University of Medical School, Japan.

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.

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