The effect of prostaglandins and indomethacin on cytotoxic T-lymphocytes and their precursors.
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(-7) M) of prostaglandin E2(PGE2) 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(-9) M) 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.
Skinner
M
M
Department of Immunobiology, School of Medicine, University of Auckland, New Zealand.
Skinner
S
S
Marbrook
J
J
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011453:Prostaglandins / Q000494:pharmacology*; D011460:Prostaglandins F / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology
D011453:Prostaglandins; D011460:Prostaglandins F; D015232:Dinoprostone; C100006:prostaglandin F1; D007213:Indomethacin