Human interleukin-10 can directly inhibit T-cell growth.
Human interleukin-10 (IL-10) inhibits T-cell proliferation and cytokine production in the presence of monocytes. In this study, we have investigated whether IL-10 can directly inhibit T cells. Highly purified peripheral blood T cells containing less than 0.1% CD14+ cells and unresponsive to phytohemagglutinin (PHA), were growth-inhibited by IL-10 when stimulated with immobilized OKT3 monoclonal antibody (MoAb; 55.4% inhibition). This effect was neutralized by the murine MoAb 19F1 directed against human IL-10. In addition, IL-10 inhibited by 52.5% the proliferation of a human tetanus toxoid-specific T-cell clone (TM11) induced by immobilized OKT3 MoAb in the absence of antigen-presenting function. T-cell growth inhibition by IL-10 did not reflect a cytokine-induced change in the kinetics of T-cell response to immobilized OKT3 MoAb, and was observed over a wide range of cell and OKT3 MoAb concentrations. Addition of 1% to 5% monocytes to highly purified peripheral blood T cells resulted in the emergence of proliferation to PHA and to soluble OKT3 MoAb, but did not significantly affect levels of growth inhibition by IL-10 in the presence of immobilized OKT3 MoAb. Similarly, addition of 10% monocytes to the TM11 T-cell clone resulted in the emergence of proliferation in response to tetanus toxoid, but did not significantly influence growth inhibition by IL-10 in the presence of immobilized OKT3 MoAb. When stimulated with immobilized OKT3 MoAb in the absence of accessory cells, T cells secreted IL-2. Secretion of IL-2 under these conditions was inhibited by IL-10 (51.5% inhibition). Thus, IL-10 can directly inhibit growth and IL-2 production in T cells triggered by immobilized OKT3 MoAb in the absence of monocytes.
Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892.
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Taga
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Mostowski
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Tosato
D017252:CD3 Complex / Q000276:immunology; D002448:Cell Adhesion; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D006131:Growth Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology
D017252:CD3 Complex; D006131:Growth Inhibitors; D007376:Interleukin-2; D013745:Tetanus Toxoid; D016753:Interleukin-10