FK506 AND CYCLOSPORINE-A EACH INHIBIT ANTIGEN-SPECIFIC SIGNALING IN THE T-CELL LINE-171 IN THE ABSENCE OF A CALCIUM SIGNAL

Antigen-specific signal transduction leading to IL2 induction and secretion in the T cell line 171 is augmented by association of p56(lck) with CD4. Although no change in cytoplasmic calcium level ([Ca2+](i)) was detectable during antigen-specific signal transduction of the 171-CD4(+) cells, IL2 induction was inhibited by FK506 and CsA. Since these drugs are thought to act selectively by inhibiting calcineurin, a calcium-calmodulin-dependent protein phosphatase associated with activation of the IL2 promoter, we considered the possibility that calcineurin is constitutively active in 171 cells. However, we found no evidence for this because PMA failed to supplement any putatively active calcineurin to induce IL2. secretion. We suggest that IL2 secretion induced by antigen presentation to TCR/CD4/p56(lck) requires an FK506 and cyclosporin A-sensitive step which may be independent of calcium signaling. Rapamycin did not inhibit IL2 secretion induced by TCR/CD4/p56(lck), emphasizing the specific action of FK506 and cyclosporin A. (C) 1994 Academic Press, Inc.