DIFFERENTIAL ABILITY OF T(H)1 AND T(H)2 T-CELLS TO EXPRESS FAS LIGAND AND TO UNDERGO ACTIVATION-INDUCED CELL

Stimulation of previously activated T cells through the antigen receptor can result in the apoptotic death of the responding cell, a process referred to as activation-induced cell death (AICD). This process appears to involve Fas (CD95) and its ligand (Fas-L). The distribution of Fas and Fas-L on Various T cell subsets has not been extensively characterized. We have therefore analyzed cells committed to a T(h)1- or T(h)2-type differentiation pattern for the expression and function of Fas-L. Using both a sensitive bioassay and flow cytometry, we demonstrate that cloned T(h)1 cells express high levels of Fas-L, whereas cloned T(h)2 cells express only low levels. The expression of Fas-L by T(h)1 and T(h)2 cells correlates with the relative abilities of these two cell types to undergo AICD. Whereas AICD is readily observed in cultures of cloned T(h)1, but not T(h)2, cells, T(h)2 cells are capable of undergoing apoptosis in the presence of T(h)1 cells expressing Fas-L. The ability of T cells to undergo AICD appears to be unrelated to the presence of various cytokines. Thus, the Fas/Fas-L pathway appears to be critical for the induction of AICD and this pathway is differentially regulated in cells committed to either T(h)1 or T(h)2 differentiation.