Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death.
Previously, we and others showed that signals relayed through the murine T cell Ag 4-1BB enhance primary T cell responses, and that blocking the interaction of 4-1BB with its ligand results in decreased responses to polyclonal activators and to alloantigens. Because 4-1BB expression is induced following primary stimulation, we investigated the role of signaling through this molecule in the reactivation of proliferating T cells. To this end, preactivated, 4-1BB-expressing T cells were restimulated in the presence of plate-immobilized mAbs directed against 4-1BB or the prototypic costimulatory molecule CD28. In this work, we show that in the presence of either signal, T cells respond to TCR cross-linking with strong proliferative responses and cytokine production; moreover, our findings indicate that T cell proliferation partially correlates with surface 4-1BB expression. In addition, our results suggest that Ab-mediated costimulatory signals can act independently of potential accessory B7-CD28/CTLA-4 (cytotoxic T lymphocyte Ag-4) interactions. Importantly, the characteristic DNA fragmentation and apoptotic cell death observed after TCR re-engagement are inhibited comparably in the presence of either 4-1BB or CD28 signaling.
Hurtado
J C
JC
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202, USA.
Kim
Y J
YJ
Kwon
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D018106:CD28 Antigens / Q000276:immunology; D016923:Cell Death / Q000276:immunology*; D053938:DNA Fragmentation / Q000276:immunology; D005260:Female; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013997:Time Factors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018106:CD28 Antigens; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505715:Tnfrsf9 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9