Tumor necrosis factor alpha and interleukin-1 alpha inhibit through different pathways interferon-gamma-induced antigen presentation, processing and MHC class II surface expression on astrocytes, but not on microglia

Astrocytes and microglia, two glial cell populations of the CNS, have been described to be involved in many immune processes. We used defined combinat ions of cytokines, interferon gamma (IFN-gamma)/interleukin-1 alpha (IL-1 a lpha) and IFN-gamma/tumor necrosis factor alpha (TNF alpha), to simulate di fferent in vitro immune environments observed in disease or inflammation. I n these conditions, we analyzed and compared the regulating effects of thes e cytokines on cell surface and total expression of MHC II and on the capac ity of murine astrocytes and microglia to present peptide and native antige ns to specific primed T cells. Neither IL-1 alpha nor TNF alpha affected th e IFN-gamma-induced antigen presentation capacity of microglia. Astrocytes, however, were severely impaired in their capacity to present native antige ns and, to a minor extent, a peptide antigen. Total expression of MHC II wa s not affected by these cytokines in microglia, whereas in astrocytes it wa s reduced by IL-1 alpha and increased by TNF alpha. Both cytokines downregu lated MHC II expression at the surface of astrocytes, but not of microglia. This shows that TNF alpha affects the of IFN-gamma- immunocompetent astroc ytes to process and present antigen, probably either by altering membrane t raffic of MHC II and of antigen and/or enzymatic activities associated with these mechanisms, while IL-1 alpha does so by downregulating MHC II expres sion. Altogether, our results illustrate how differently astrocytes and mic roglia react toward a defined, similar immune environment. One type of cell , the astrocytes, downregulate their T-cell stimulation and MHC II traffick ing, and probably also their antigen processing, functions while the other, the microglia, maintain their antigen presentation potential.