The effect of prostaglandins and indomethacin on cytotoxic T-lymphocytes and their precursors

Abstract

The effect of prostaglandins of the E and F series on the generation of cytotoxic T-lymphocytes (CTL) was investigated. High concentrations (10 −6−10 −7M) of prostaglandin E2(PGE 2 inhibited the generation of both antigen-specific CTL and “activated” killers from precursor cells. Virtually no effect on the growth and cytotoxic activity of antigen-specific CTL clones was detectable. As with prostaglandins of the F series, lower concentrations of the E series (10 −8−10 −9M) enhanced the generation of antigen-specific CTL but inhibited the generation of lymphokine and spontaneously-activated CTL. When endogenous PG production was blocked with indomethacin, the generation of antigen-specific CTL was enhanced in bulk culture. Indomethacin also increased the frequency of allo-reactive CTL precursors and in anti-fluorescein responses it created conditions in which suppression was overridden. These results indicate that prostaglandins can exert both negative and positive regulatory effects on an antigen-specific cytotoxic response and can influence the apparent specificity of the cytotoxic cells that are generated.