HDL Interfere with the Binding of T Cell Microparticles to Human Monocytes to Inhibit Pro-Inflammatory Cytokine Production

BACKGROUND: Direct cellular contact with stimulated T cells is a potent mechanism that induces cytokine production in human monocytes in the absence of an infectious agent. This mechanism is likely to be relevant to T cell-mediated inflammatory diseases such as rheumatoid arthritis and multiple sclerosis. Microparticles (MP) generated by stimulated T cells (MP(T)) display similar monocyte activating ability to whole T cells, isolated T cell membranes, or solubilized T cell membranes. We previously demonstrated that high-density lipoproteins (HDL) inhibited T cell contact- and MP(T)-induced production of IL-1β but not of its natural inhibitor, the secreted form of IL-1 receptor antagonist (sIL-1Ra). METHODOLOGY/PRINCIPAL FINDINGS: Labeled MP(T) were used to assess their interaction with monocytes and T lymphocytes by flow cytometry. Similarly, interactions of labeled HDL with monocytes and MP(T) were assessed by flow cytometry. In parallel, the MP(T)-induction of IL-1β and sIL-1Ra production in human monocytes and the effect of HDL were assessed in cell cultures. The results show that MP(T), but not MP generated by activated endothelial cells, bond monocytes to trigger cytokine production. MP(T) did not bind T cells. The inhibition of IL-1β production by HDL correlated with the inhibition of MP(T) binding to monocytes. HDL interacted with MP(T) rather than with monocytes suggesting that they bound the activating factor(s) of T cell surface. Furthermore, prototypical pro-inflammatory cytokines and chemokines such as TNF, IL-6, IL-8, CCL3 and CCL4 displayed a pattern of production induced by MP(T) and inhibition by HDL similar to IL-1β, whereas the production of CCL2, like that of sIL-1Ra, was not inhibited by HDL. CONCLUSIONS/SIGNIFICANCE: HDL inhibit both MP(T) binding to monocytes and the MP(T)-induced production of some but not all cytokines, shedding new light on the mechanism by which HDL display their anti-inflammatory functions.