Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death.

JC Hurtado, YJ Kim, BS Kwon - Journal of immunology (Baltimore …, 1997 - journals.aai.org
JC Hurtado, YJ Kim, BS Kwon
Journal of immunology (Baltimore, Md.: 1950), 1997journals.aai.org
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 …
Abstract
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.
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