REQUIREMENT OF FAS(CD95), CD45, AND CD11A CD18 IN MONOCYTE-DEPENDENT APOPTOSIS OF HUMAN T-CELLS/

Our previous studies demonstrated that upon activation, monocytes (Mo) were able to sensitize peripheral blood T (PBT) cells to apoptosis in duced by treatment with PMA. However, it is unknown what gene products provide the death signal to the sensitized PBT cells and how activate d Mo enable PBT cells to become susceptible to apoptosis. Here, we sho w that PBT cells, but not Mo, express functional Fas ligand upon treat ment with PMA. Moreover, this Mo-dependent T cell apoptosis could be b locked by a Fas-Ig fusion protein, as well as by a nonlytic mAb agains t Fas molecule. These results strongly suggest involvement of Fas-Fas ligand interaction in the death of PBT cells. Unlike Fas-induced apopt osis, however, Mo-dependent T cell death was completely inhibited by o verexpression of the Bcl-2 protein, and PMA alone was sufficient to tr igger apoptosis in T cells when Mo were included in culture. Furthermo re, anti-CD11a, anti-CD18, or anti-CD45/CD45RA mAbs could prevent PBT cells from death triggered by PMA plus Mo, suggesting that these Ags p articipate in the apoptotic process. The participation of CD45RA in th e death of PBT cells was further demonstrated by the observation that the J45.01 cell line, a CD45-deficient variant of Jurkat cells, did no t undergo apoptosis by this Mo-dependent mechanism. When transfected w ith cDNA encoding CD45RA, J45.01 cells acquired apoptotic response to PMA stimulation in the presence of Mo to a similar, but lesser, degree than normal Jurkat cells.