The role of caspase 3 and BclxL 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 examined, IL-7 (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA profile and fragmentation. IL-2 also acted as a mitogen in these T cells, Both cytokines abrogated the dexamethasone-induced 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 dexamethasone, but Bcl-2 was expressed at a much lower level than BclxL in these cells. Levels of Bas did not markedly change on either cytokine stimulation or dexamethasone treatment. An unidentified 23-kDa band, which was recognized by the anti-Bcl-2 antibody, was induced by dexamethasone and suppressed by IL-7 and IL-2, This protein was subject to independent regulation as compared to the p26 Bcl-2 protein, suggesting that it may be a novel factor, possibly involved in the regulation of apoptosis, A clear role for IL-7 as a survival factor for cytokine withdrawal and glucorcorticoid induced apoptosis in activated primary hT cells is implicated. In addition, regulation of Bclx(L) and downstream inhibition of Caspase 3 activity may mediate this rescue signal. (C) 1998 Academic Press.