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.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Immunology|
|State||Published - Jan 1 1982|
ASJC Scopus subject areas
- Immunology and Allergy