Microglia are essential for T cell activation in the CNS. Since T cell activation requires costimulation by B7 and/or CD40, we examined the regulation by cytokines of B7-1, B7-2 and CD40 mRNA expression in cultured rat microglia in serum-foe medium. All three ligands are expressed constitutively, but are profoundly up-regulated by granulocyte-macrophage colony-stimulating factor (GEL I-CSF). By contrast, interferon-gamma raises only B7-2 and CD30 mRNA, and the B7-2 increase is inhibited by IL-10. IL-4, transforming growth factor-beta 1, and nerve growth factor (NGF) repress GM-CSF-induced B7-2 and CD40, but not B7-1. NGF also down-regulates its own high-affinity trkA receptor. IL-11, unrecognized for its effect on antigen presentation, represses GM-CSF-induced B7-2. (C) 1999 Elsevier Science B.V. All rights reserved.