Activation-induced cell death of human T-cell subsets is mediated by Fas and granzyme B but is independent of TNF-α

• Published in: Journal of leukocyte biology Vol. 70; no. 5; pp. 756 - 766
• Main Authors: Gorak‐Stolinska, Patricia, Truman, Jean‐Philip, Kemeny, David M., Noble, Alistair
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.11.2001
• Subjects: Adult; Amino Acid Chloromethyl Ketones - pharmacology; Anti-Bacterial Agents - pharmacology; apoptosis; Calcium; Caspase 8; Caspase 9; Caspase Inhibitors; CD4; CD8; Chelating Agents - pharmacology; Cytoplasmic Granules - secretion; Egtazic Acid - pharmacology; Enzyme Inhibitors - pharmacology; Etanercept; Exocytosis; Fas antigen; Fas Ligand Protein; fas Receptor - physiology; granzyme B; Granzymes; Humans; Immunoglobulin G - pharmacology; Interferon-gamma - secretion; Interleukin-12 - pharmacology; Interleukin-2 - pharmacology; Interleukin-4 - secretion; Lymphocyte Activation; Macrolides; Membrane Glycoproteins - antagonists & inhibitors; Membrane Glycoproteins - physiology; Muromonab-CD3 - pharmacology; perforin; Receptors, Tumor Necrosis Factor - physiology; Recombinant Fusion Proteins - physiology; Recombinant Proteins - pharmacology; Serine Endopeptidases - physiology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - secretion; Th1 Cells - cytology; Th1 Cells - drug effects; Th1 Cells - immunology; Th1 Cells - secretion; Th2 Cells - cytology; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - secretion; TNFR; tumor necrosis factor receptors; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.70.5.756

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.