Differential regulation of bcl-2 and bcl-x by CD3, CD28, and the IL-2 receptor in cloned CD4+ helper T cells. A model for the long-term survival of memory cells.
In this study, we examined the molecular signals that control apoptosis in cloned CD4+ helper T cells. Resting T cells were highly resistant to spontaneous death in the absence of exogenous stress, and they expressed low levels of bcl-x protein and no detectable bcl-2. Upon exposure to gamma radiation, resting cells rapidly underwent apoptotic death. Incubation with IL-2 prevented this cell death and led to a large increase in bcl-2 protein expression and only a modest up-regulation in bcl-x. The combination of anti-CD3 and anti-CD28 mAbs was also effective in protecting the cells against radiation-induced apoptosis; however, this protection was associated predominantly with bcl-x up-regulation, and only a small induction of bcl-2 protein was observed. Finally, cyclosporin A blocked both IL-2 secretion and bcl-2 induction in response to CD3 plus CD28 stimulation, suggesting a role for endogenous lymphokine production in the induction of bcl-2. These data support a model in which memory T cells remain resistant to apoptosis because intermittent contact with Ag-bearing APC and IL-2R occupancy result in the expression of the life-proteins bcl-2 and bcl-x.
Mueller
D L
DL
Department of Medicine, Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
Seiffert
S
S
Fang
W
W
Behrens
T W
TW
D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000528:radiation effects; D017252:CD3 Complex / Q000187:drug effects / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000528:radiation effects; D002470:Cell Survival / Q000276:immunology; D002999:Clone Cells; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology*; D007156:Immunologic Memory; D007376:Interleukin-2 / Q000502:physiology; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D017252:CD3 Complex; D007376:Interleukin-2; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2; D051020:bcl-X Protein; D016572:Cyclosporine; D011505:Protein-Tyrosine Kinases