title: Immune regulation by platelet-activating factor. I. Induction of suppressor cell activity in human monocytes and CD8+ T cells and of helper cell activity in CD4+ T cells.
abstract: Platelet-activating factor (PAF) is a powerful mediator of inflammation. We have recently described a potential role for PAF in immune reactions, as it inhibits T cell proliferation and IL-2 production in response to mitogens. To further define the mechanism through which this inhibition is exerted, we used a coculture system in which PBML are preincubated with increasing concentrations of PAF for 24 h, followed by washing, treatment with mitomycin C and addition to fresh autologous PBML stimulated with PHA. In this context, a significant (40 to 60%) inhibition of proliferation was observed. In parallel, PAF-pre-treated cells induced a reduction (30 to 50%) of IL-2 production by PHA-stimulated lymphocytes. The PAF receptor antagonist BN52021 could partially block the PAF-induced suppressor cell activity, but also showed some suppressor cell-inducing properties of its own (20 to 30%). The expression of suppressor cell function during the co-culture could be partially abrogated by the inclusion of indomethacin, suggesting that cycloxygenase metabolites of arachidonic acid were involved in this phase of suppression. When PBML were fractionated into monocytes, lymphocytes, or T cell subsets before pre-incubation with PAF, indomethacin-sensitive suppressor cell function was generated in the monocyte population. Monocyte-depleted lymphocytes showed slight helper effect, whereas CD8+ T cells were induced to become indomethacin-resistant suppressor cells. CD4+ T cells, in contrast, were activated to exert very marked helper effect. When incubated with PAF for 24 h, monocyte-depleted lymphocytes showed a 30% decrease in CD4+ T cell numbers and a 50% increase in CD8+ T cell numbers. Our data suggest a novel immunoregulatory role for PAF and potentially important interactions of this lipid mediator of inflammation with lymphocyte and monocyte functions.
authors.affiliation: Department of Pediatrics, University of Sherbrooke, Quebec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Rola-Pleszczynski
authors.forename: C
authors.initials: C
authors.lastname: Pouliot
authors.forename: S
authors.initials: S
authors.lastname: Turcotte
authors.forename: B
authors.initials: B
authors.lastname: Pignol
authors.forename: P
authors.initials: P
authors.lastname: Braquet
authors.forename: L
authors.initials: L
authors.lastname: Bouvrette
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D010641:Phenotype; D010972:Platelet Activating Factor / Q000378:metabolism / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000145:classification / Q000187:drug effects / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D011451:Prostaglandin-Endoperoxide Synthases