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Activation‐induced cell death of human T‐cell subsets is mediated by Fas and granzyme B but is independent of TNF‐α
Author(s) -
GorakStolinska Patricia,
Truman JeanPhilip,
Kemeny David M.,
Noble Alistair
Publication year - 2001
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.70.5.756
Subject(s) - granzyme b , granzyme , biology , apoptosis , programmed cell death , fas receptor , microbiology and biotechnology , exocytosis , tumor necrosis factor alpha , t cell , perforin , immunology , secretion , antigen , immune system , cd8 , endocrinology , biochemistry
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‐α/TNFR interactions because although type 1 cells secreted more TNF‐α 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.