Several cysteine and serine protease inhibitors previously shown to bl
ock TCR-induced death of 2B4 T hybridoma cells were tested for their a
bility to block various T lymphocyte apoptotic death systems. TCR-indu
ced death of both peripheral CD4(+) and CD8(+) T cell blasts was inhib
ited similarly to the hybridoma, but cell death in these cells induced
by anti-Fas, gamma-irradiation, etoposide, or extracellular ATP was n
ot blocked. For T cell lines, cell death induced by CTL or by IL-2 wit
hdrawal was also not inhibited. TCR-induced death oi immature CD4(-)8(
+) thymocytes triggered by culture on immobilized anti-CD3 was not blo
cked by these protease inhibitors, whereas similar death induced in th
e resting CD4(+)8(-) thymocyte subset under these conditions was inhib
ited similarly to the T cell blasts. TCR-induced proliferation of the
latter subset was modest in the absence of oxogeneous IL-2, but was en
hanced two- to fourfold by the protease inhibitors. These results show
that a protease-dependent death pathway can be triggered by the TCR i
n mature T cells; similar protease-dependent steps are not common to t
he TCR-triggered activation pathway or other apoptotic death pathways
in these cells.