Macrophage-derived nitric oxide inhibits the proliferation of activated T helper cells and is induced during antigenic stimulation of resting T cells

To examine how macrophage-derived nitric oxide (NO) affects T helper (Th) c ell activity, T cell clones representing Th1 and Th2 subsets were activated before exposure to stimulated peritoneal macrophages or microglia. Both Th subsets were similarly sensitive to inhibition by NO, indicating that macr ophage-derived NO regulates the proliferation of activated Th1 and Th2 cell s equally well. Since IFN-gamma production remained intact in NO-treated Th 1 cells, we studied whether NO was produced during antigen-specific activat ion of Th1 cells by unstimulated macrophages. Indeed, T cell proliferation only occurred when a NO synthase inhibitor was included, while IFN-gamma wa s essential for the induction of NO. These studies demonstrate that macroph ages produce NO following antigen presentation to Th1 cells and that macrop hage-derived NO inhibits Th1 and Th2 cell proliferation without inhibiting cytokine production. (C) 2000 Academic Press.