Activation-induced cell death of human T-cell subsets is mediated by Fas and granzyme B but is independent of TNF-alpha.
Gorak-Stolinska, P;
Truman, JP;
Kemeny, DM;
Noble, A;
(2001)
Activation-induced cell death of human T-cell subsets is mediated by Fas and granzyme B but is independent of TNF-alpha.
Journal of leukocyte biology, 70 (5).
pp. 756-766.
ISSN 0741-5400
DOI: https://doi.org/10.1189/jlb.70.5.756
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Human primary effector T cells were analyzed for their susceptibility to anti-CD3-induced activation-induced cell death (AICD). Th1 and Tc1 cells were more susceptible to AICD than their type 2 counterparts. Type 1 and type 2 subsets were also found to be differentially susceptible to CD95-mediated apoptosis, although cell-surface expression of CD95 and CD95L was at similar levels on all subsets. A role for CD95 in AICD was confirmed by the addition of anti-CD95L antibodies that partially abrogated AICD. Residual apoptosis could not be accounted for by TNF-alpha/TNFR interactions because although type 1 cells secreted more TNF-alpha than type 2 cells, the addition of TNFR:Fc fusion protein did not inhibit AICD. Instead, a reduction in AICD was observed in the presence of EGTA or concanamycin A. The inhibition of apoptosis by a granzyme B inhibitor z-AAD-CMK in Tc1 cells further indicated an involvement of the granule exocytosis mechanism in AICD.