Prostaglandin E2 mediates subset-specific effects on the functional responses of allosensitized T lymphocyte clones.
The release of potent immunoregulatory substances in the mixed inflammation of a rejecting allograft could significantly modify the accumulation and subsequent function of the infiltrating lymphocyte population. Prostaglandin E2 (PGE2) is a major cyclooxygenase metabolite of arachidonic acid that is released at sites of inflammation in vivo at concentrations reported to inhibit the functional responses of bulk lymphocyte populations. In order to more directly assess the role of PGE2 as a modulator of the immune response, we examined its effects on in vitro lymphocyte random migration (using a modified Boyden chamber assay), proliferation to a variety of stimuli, and both allospecific and lectin-mediated cytotoxicity using several C57BL/6 anti DBA/2 T cell clones characterized functionally as helper (n = 5), cytotoxic (CTL, n = 4), or cytotoxic only in the presence of lectin (L-CTL, n = 1). Helper cell migration and proliferation to secondary MLC supernatant or recombinant IL-2 were inhibited (P less than 0.001) by physiologic concentrations (10-100 ng/ml) of PGE2. In contrast, the migration, proliferation and cytotoxicity of all lytic clones (CTL or L-CTL) were not affected by these or higher concentrations (1000 ng/ml) of PGE2. Indomethacin (10(-6) M) did not modify lymphocyte responses to PGE2. The effects of PGE2 on helper cell function were completely reversible by cell washing. These data show that the effector functions of cloned T cells are inhibited by PGE2 in a subset-specific fashion fashion and suggest that components of immunologically initiated inflammation may play a heretofore unrecognized role in locally modulating the behavior of distinct T cell subsets at the rejecting allograft.
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015232:Dinoprostone; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D011458:Prostaglandins E / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects
D011458:Prostaglandins E; D015232:Dinoprostone