Regulation of the IL-10 Production by Human T Cells

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Abstract
Interleukin (IL)‐10, an immunomodulatory cytokine predominantly produced by monocytes/macrophages and T cells, inhibits several functions of dendritic cells (DC), monocytes and T cells including their cytokine production, but it stimulates B cell immunoglobulin (Ig) production and cytotoxic T lymphocyte (CTL) generation. A precise knowledge of the mechanisms that control the IL‐10 production is therefore highly important for understanding the immunoregulation. The IL‐10 production was studied in cultures of freshly isolated human T cells. A rise in intracellular calcium as well as the common γ‐chain containing cytokine receptor triggering or CD28 triggering were found to be important signals for IL‐10 induction. CD80, CD58, rIL‐12 and rIFN‐α all had efficacious and independent costimulatory activities on the IL‐10 production, while PGE2 was inhibitory. Dependence on autocrine IL‐2 signalling was shown by the effects of anti‐IL‐2 and anti‐IL‐2R monoclonal antibodies (MoAb), but the IL‐10 production proceeded partly IL‐2‐independent when CD80 provided costimulation. Sensitivity to inhibition by CsA was not removed by CD80 or CD58 costimulation and/or by addition of rIL‐12 or rIFN‐α, pointing to the absolute requirement for calcineurin activity. These data reveal important differences in the regulatory pathways between IL‐10 (a cytokine‐inhibitory interleukin) and IL‐2 (a cytokine‐inducing interleukin), which can potentially be exploited therapeutically. The fact that CsA blocks the production of IL‐10, which itself has important immunosuppressive properties, should be taken into account in defining immunosuppressive treatment schedules which include the use of CsA.