CD9-mediated costimulation of TCR-triggered naive T cells leads to activation followed by apoptosis.
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.
Tai
X G
XG
Biomedical Research Center, Osaka University of Medical School, Japan.
Toyooka
K
K
Yashiro
Y
Y
Abe
R
R
Park
C S
CS
Hamaoka
T
T
Kobayashi
M
M
Neben
S
S
Fujiwara
H
H
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060245:Tetraspanin 29; D051020:bcl-X Protein
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; C494812:Bcl2l1 protein, mouse; C554870:Cd9 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011948:Receptors, Antigen, T-Cell; D060245:Tetraspanin 29; D051020:bcl-X Protein