ANTIGEN PRESENTATION IN THE CENTRAL-NERVOUS-SYSTEM - THE INHIBITORY EFFECT OF IL-10 ON MHC CLASS-II EXPRESSION AND PRODUCTION OF CYTOKINES DEPENDS ON THE INDUCING SIGNALS AND THE TYPE OF CELL ANALYZED

Cells of the macrophage lineage are required to cope with bacterial in fection and to serve as APC for T lymphocytes. Among the regulatory fa ctors limiting the macrophage response to infection and the expansion of Ag-specific T cells, IL-10 has received recent attention. On monocy tes/macrophages, IL-10 has been shown to inhibit the intracellular kil ling of bacteria, the secretion of cytokines, and the expression of MH C molecules. In the present study we have examined the effect of IL-10 on different APC obtained from the central nervous system. Both, astr ocytes and microglial cells are in a resting state and require activat ion signals to express MHC class II and cytokine genes. Whereas IL-10 profoundly inhibits the IFN-gamma-induced expression of MHC class II A g on microglial cells, it had no such effects on astrocytes. Neverthel ess, IL-10 suppressed the MHC class II- and Ag-dependent proliferative response of T cells in the presence of both types of APC. As shown by the use of anti-IL-10 Abs, endogenously produced IL-10 influenced the function of microglia but not of astrocytes to serve as APC. IL-10 si gnificantly inhibited the LPS-induced production of granulocyte-macrop hage-CSF, macrophage-CSF, and IL-6 by both astrocytes and microglial c ells. In contrast, the secretion of these cytokines by the two glial c ell population was not altered by IL-10 when IL-1 beta, TNF-alpha, or viruses were used as stimuli.