Jc. Hurtado et al., SIGNALS THROUGH 4-1BB ARE COSTIMULATORY TO PREVIOUSLY ACTIVATED SPLENIC T-CELLS AND INHIBIT ACTIVATION-INDUCED CELL-DEATH, The Journal of immunology, 158(6), 1997, pp. 2600-2609
Previously, we and others showed that signals relayed through the muri
ne T cell Ag 4-1BB enhance primary T cell responses, and that blocking
the interaction of 4-1BB with its ligand results in decreased respons
es to polyclonal activators and to alloantigens. Because 4-1BB express
ion is induced following primary stimulation, we investigated the role
of signaling through this molecule in the reactivation of proliferati
ng T cells. To this end, preactivated, 4-1BB-expressing T cells were r
estimulated 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 cr
oss-linking with strong proliferative responses and cytokine productio
n; moreover, our findings indicate that T cell proliferation partially
correlates with surface 4-1BB expression. In addition, our results su
ggest that Ab-mediated costimulatory signals can act independently of
potential accessory B7-CD28/CTLA-4 (cytotoxic T lymphocyte Ag-4) inter
actions. Importantly, the characteristic DNA fragmentation and apoptot
ic cell death observed after TCR re-engagement are inhibited comparabl
y in the presence of either 4-1BB or CD28 signaling.