The effects of prostaglandins on the proliferation of cultured human T lymphocytes.
The effects of PGE2 on cultured T lymphocytes (CTC) stimulated by either Con A, PHA, or lectin-free IL-2 were studied. PGE2, in a concentration ranging from 100 to 1 ng/ml, consistently and significantly inhibited the proliferation of CTC induced by either PHA or Con A. PGF2 alpha was essentially without effect. Although the degree of inhibition of PHA-treated CTC was increased with suboptimal amounts of PHA, significant inhibition still resulted with optimal PHA concentrations. PGE2, but not PGF2 alpha, was also effective in significantly inhibiting the proliferation of IL-2-treated CTC in a dose-related fashion; however, the addition of suboptimal amounts of IL-2 did not result in greater increases in the degree of inhibition by PGE2. Depleting the CTC of either OKT-4 or OKT-8 phenotypic cells did not abrogate this PGE2 inhibitory effect, indicating that PGE2 does not suppress the proliferative response solely by the activation of suppressor cells with the OKT-8 phenotype. PGE2 also was found to inhibit the production of IL-2 by fresh lymphocytes treated by either optimal or suboptimal amounts of PHA, however, this decrease in production by PGE2 was not necessarily associated with a decrease in the proliferation of these stimulated lymphocytes. Only with low PHA concentrations, where IL-2 production was markedly reduced and barely detectable, was lymphocyte proliferation appreciably reduced by PGE2. In additional experiments, LiCl was added to PGE2 containing cultures to determine whether LiCl could modulate the inhibitor effect of PGE2 of either PHA- or IL-2-stimulated CTC. In these studies, LiCl, in concentrations of 1-10 mM was found to lessen or completely abrogate the reduced PHA proliferative response induced by PGE2. This effect was more pronounced with suboptimal concentrations of PHA than with optimal PHA amounts. In contrast, the PGE2-induced inhibition of IL-2-stimulated CTC was not modified or altered by the addition of LiCl. Thus, these results suggest that LiCl acts at the level of IL-2 production instead of IL-2 action, and that PGE2 inhibits IL-2-induced proliferation of CTC by a different or additional mechanism than for PHA-treated cells. In conclusion, these results, taken as a whole, indicate that PGE2 suppresses the proliferation of stimulated CTC by at least two different mechanisms: 1) by reducing the production of IL-2 by stimulated lymphocytes; and 2) by directly acting on the responding CTC.(ABSTRACT TRUNCATED AT 400 WORDS)
D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D015232:Dinoprostone; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000276:immunology; D008094:Lithium / Q000494:pharmacology; D018021:Lithium Chloride; D008213:Lymphocyte Activation / Q000187:drug effects*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*
D002712:Chlorides; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011458:Prostaglandins E; D003208:Concanavalin A; D008094:Lithium; D018021:Lithium Chloride; D015232:Dinoprostone