A comparison of PGE₂ effects on human suppressor cell function and on interleukin 2 function

Two possible mechanisms of prostaglandin E₂- (PGE₂) mediated inhibition of human blood mononuclear cell (PBMC) proliferation were compared to determine whether PGE₂ suppressed these responses indirectly by activation of a suppressor cell, directly by inhibition of interleukin 2 (IL 2) responses, or by a combination of the two mechanisms. The first mechanism is unlikely since depletion of phenotypically defined suppressor cell populations (T(G⁺) or OKT8⁺ cells) from PMBC did not diminish the PGE₂-mediated inhibition of PHA responses. For example, 10 ng/ml PGE₂ suppressed the response of ER⁺T cells by an average of 61%, and the response of T(G^-) cells was suppressed by an average of 62%. Similarly, 10 ng/ml PGE₂ suppressed the PHA response of OKT8^- PBMC by an average of 40% and the response of unseparated PBMC by an average of 34%. Experiments were then performed to distinguish direct effects of PGE₂ from possible suppressor cell activation. PBMC were precultured with PGE₂ for 24 hr, washed, and tested for suppressor cell function in the absence of additional PGE₂. PBMC precultured with PGE₂ did not suppress the PHA response of freshly isolated autologous PBMC, whereas PBMC precultured with Con A (a positive control) suppressed the PHA response of fresh PBMC by an average of 47%. The influence of PGE₂ on IL 2-dependent proliferation and IL 2 production was then examined. PGE₂ inhibited proliferation of IL 2-dependent cell lines as measured by enumeration of viable cells and by ³H-thymidine incorporation. In addition, PGE₂ suppressed the quantity of IL 2 produced by PHA-stimulated PBMC. For example, 10 ng/ml PGE₂ reduced by 50% the amount of IL 2 activity produced by PBMC. We conclude that PGE₂ directly suppressed human lymphocyte proliferation by interfering with both the production of IL 2 and IL 2-dependent proliferation. Furthermore, there was no evidence that PGE₂ induced suppressor cell function in man.