Prostaglandin E modulation of the mitogenic response of human T cells. Differential response of T-cell subpopulations.
Prostaglandins (PG) of the E series, PGE(1) and PGE(2) (PGEs), can induce elevations of intracellular cyclic AMP (cAMP) among thymus-derived (T) lymphocytes (T cells) and inhibit their reactivity. For example, 0.1 muM of PGEs induces a two- to threefold increase of intracellular cAMP among human peripheral blood T cells and a 20-30% suppression of their blastogenic response to phytohemagglutinin. However, this suppression actually represents the net reactivity of T-cell populations demonstrating quite different responses to PGEs. Fractionation of T-enriched populations on a discontinuous density gradient yields a population of high density cells whose phytohemagglutinin-induced blastogenic response is suppressed 60%; a population of intermediate density cells whose response is suppressed 20%; and a population of low density T cells whose response is not suppressed, but is enhanced 20% by both of the PGEs. The diametrically opposite responses of low and high density T cells to the PGEs is not related to any difference in their intrinsic mitogen reactivity nor is it influenced by interactions with other T cells, bone marrow-derived (B) cells, or monocytes. Moreover, the distinct blastogenic response of low and high density T cells to PGEs does not simply correlate with PGE-mediated activation of adenylate cyclase. PGE(2) induced comparable absolute and identical relative increases of intracellular cAMP among the low and high density T cells. Cholera toxin, a potent activator of adenylate cyclase, and exogenous 8-bromo cAMP mimicked the effects of the PGEs on these two T-cell populations. These data demonstrate that T cells are heterogeneous with regard to their response to the PGEs. Thus, PGEs should be considered as potential regulators rather than as universal suppressors for T-cell reactivity. Moreover, the effect of PGEs on the blastogenic response of a given T-cell population depends upon intracellular events which occur subsequent to elevations of cAMP.
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D002458:Cell Fractionation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003864:Depression, Chemical; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D010835:Phytohemagglutinins; D011459:Prostaglandins E, Synthetic; D000242:Cyclic AMP