Mechanisms of IL-10 production in human microglia-T cell interaction

IL-10, a cytokine with important anti-inflammatory properties, is generated within the CNS during neuroinflammation, The mechanism for its production is poorly understood. Since infiltrating lymphocytes come into close proxim ity with the macrophagelike cells of the CNS, the microglia, we have used a n in vitro human microglia-T cell coculture system to address the mechanism s of IL-10 production, We demonstrate that microglia or activated T cells a lone secrete negligible amounts of IL-10, but that their coculture results in significant IL-10 production, which was effected by both cell types. IL- 10 generation was cell contact dependent, and treatment with anti-CD40, CTL A-4-Fc, or anti-CD23 decreased the IL-10 content in microglia-T cell cocult ures. The combination of anti-CD40 and CTLA-4-Fc reduced IL-10 levels to th e negligible amounts seen with T cells or microglia in isolation. By also m easuring TNF-a: levels, specificity of cytokine regulation was observed; wh ile anti-CD40 and CTLA-4-Fc reduced IL-10 and TNF-alpha levels, anti-CD23 d id not affect TNF-alpha while attenuating IL-10 generation, Anti-very late Ag-4, which decreased TNF-alpha levels, did not affect IL-10. These results implicate the CD40, B7, and CD23 pathways in IL-10 production following mi croglia-T cell encounter and have relevance to the regulation of an anti-in flammatory response within the CNS.