Differential ability of Th1 and Th2 T cells to express Fas ligand and to undergo activation-induced cell death

Stimulation of previously activated T cells through the antigenreceptor can result in the apoptotic death of the respondingcell, a process referred to as activation-induced cell death(AICD). This process appears to involve Fas (CD95) and tts ligand(Fas-L). The distribution of Fas and Fas-L on various T cellsubsets has not been extensively characterized. We have thereforeanalyzed cells committed to a T_h1- or T_h2-type differentiationpattern for the expression and function of Fas-L. Using botha sensitive bloassay and flow cytometry, we demonstrate thatcloned T_h1 cells express high levels of Fas-L, whereas clonedT_h cells express only low levels. The expression of Fas-L byT_h1 and T_h2 cells correlates with the relative abilities ofthese two cell types to undergo AICD. Whereas AICD is readilyobserved in cultures of cloned T_h1, but not T_h2 cells, T_h2 cellsare capable of undergoing apoptosls in the presence of T_h1 cellsexpressing Fas-L The ability of T cells to undergo AICD appearsto be unrelated to the presence of various cytokines. Thus,the Fas/Fas-L pathway appears to be critical for the inductionof AICD and this pathway is differentially regulated in cellscommitted to either T_h1 or T_h2 differentiation.