Differential ability of T cell subsets to undergo activation-induced cell death.
Human T cell clones were analyzed for their susceptibility to activation-induced cell death (AICD) in response to CD3/T cell receptor ligation. AICD was observed only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD. Analysis of a panel of Th0 clones, characterized by their ability to secrete both Th1 and Th2 cytokines, revealed that this subset included both AICD-sensitive (type A) and -resistant (type B) clones. Resistance to AICD by Th2 and Th0-type B clones was not due to lack of expression of either Fas receptor or its ligand. Paradoxically, the AICD-resistant clones were susceptible to apoptosis when Fas receptor was directly ligated by anti-Fas antibodies. However, prior activation of the resistant clones by monoclonal antibodies to CD3/TCR complex induced resistance against Fas-mediated apoptosis. Thus, the Fas-FasL pathway is critical for the induction of AICD in T cells, and moreover this pathway can be negatively regulated in the AICD-resistant clones by signals that are generated from ligation of the CD3/TCR complex.
Varadhachary
A S
AS
Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA 19140, USA.
Perdow
S N
SN
Hu
C
C
Ramanarayanan
M
M
Salgame
P
P
D000938:Antigen-Presenting Cells / Q000276:immunology; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D053222:Fas Ligand Protein; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014373:Tuberculin / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D013745:Tetanus Toxoid; D014373:Tuberculin; D019014:fas Receptor