THE ROLE OF CASPASE-3 AND BCLX(L) IN THE ACTION OF INTERLEUKIN-7 (IL-7) - A SURVIVAL FACTOR IN ACTIVATED HUMAN T-CELLS

The effects of interleukin 7 (IL-7) on apoptosis in interleukin 2 (IL- 2)-dependent, activated, primary, human T lymphocytes (hT cells) was e xamined, IL-7 (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA profile and fragmentation. IL-2 also acted as a mi togen in these T cells, Both cytokines abrogated the dexamethasone-ind uced stimulation of Caspase 3 and prevented the cleavage of poly (ADP- ribose) polymerase (PARP), a substrate for Caspase 3, IL-7 upregulated the expression of Bclx(L) and counteracted the downregulation of this anti-apoptotic protein by the synthetic glucocorticoid, dexamethasone . Bcl-2 protein expression was upregulated by IL-7 with or without dex amethasone, but Bcl-2 was expressed at a much lower level than BclxL i n these cells. Levels of Bas did not markedly change on either cytokin e stimulation or dexamethasone treatment. An unidentified 23-kDa band, which was recognized by the anti-Bcl-2 antibody, was induced by dexam ethasone and suppressed by IL-7 and IL-2, This protein was subject to independent regulation as compared to the p26 Bcl-2 protein, suggestin g that it may be a novel factor, possibly involved in the regulation o f apoptosis, A clear role for IL-7 as a survival factor for cytokine w ithdrawal and glucorcorticoid induced apoptosis in activated primary h T cells is implicated. In addition, regulation of Bclx(L) and downstre am inhibition of Caspase 3 activity may mediate this rescue signal. (C ) 1998 Academic Press.