Control of human T cell proliferation by platelet-activating factor.
Platelet-activating factor, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF), is a membrane phospholipid with immunomodulatory functions. We studied the influence of PAF on mitogen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC), purified T cells and T cell subsets. High concentrations of PAF suppressed the proliferation of all cell populations studied (44% mean inhibition with 5 microM PAF and 78% inhibition with 10 microM PAF). In contrast, the deacetylated metabolite of PAF, lyso-PAF, had no effect on proliferation at micromolar concentrations. Lower, and presumably physiologically relevant, concentrations of PAF (10(-14) to 10(-8) M) stimulated a small increase in the proliferation of unfractionated T cells. When T cells were fractionated into CD4+ and CD8+ subsets, a difference in sensitivity to PAF was observed. PAF stimulated a modest, yet statistically significant, increase in the proliferation of CD4+ T cells at concentrations ranging from 10(-14) to 10(-10) M, while either having no effect or inhibiting the proliferation of CD8+ cells across the entire concentration range. Addition of indomethacin to the cultures further enhanced CD4+ proliferation, possible due to the blockade of PAF-induced PGE2 production by monocytes. The PAF receptor antagonist BN 52021 did not block the PAF effects in this system, and the PAF receptor antagonist SRI 63-675 caused a dose dependent inhibition of T cell subset proliferation. These findings suggest that while high concentrations of PAF suppress T cell proliferation, low concentrations selectively stimulate proliferation of the CD4+ subset, an effect which is partially counteracted by PAF-induced monocyte PGE2 production.
Behrens
T W
TW
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Goodwin
J S
JS
D000328:Adult; D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D002455:Cell Division / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D010972:Platelet Activating Factor / Q000502:physiology*; D012756:Sheep; D013601:T-Lymphocytes / Q000187:drug effects*
D015704:CD4 Antigens; D010972:Platelet Activating Factor; D007213:Indomethacin