Cultured murine parenchymal liver cells induce differentiation of bone marrow cells to macrophage-like cells which present antigen to Th1 clones but inhibit their proliferation by nitric oxide and prostaglandins

Suppressor cells were developed from nylon wool nonadherent CD4(-)8(-)TCR b eta(-) bone marrow cells cocultured with parenchymal liver cells for 2.5 da ys. The major suppressor cell population consisted of nylon wool/plastic di sh-adherent, phagocytic Mac-1(+) CD3(-)4(-)8(-) cells (Ad cells), with 34% of the Ad cells being F4/80(+). These Ad cells suppressed the antigen-speci fic proliferation of Th1 clones in an MHC-nonrestricted manner. They showed a dose-dependent increase in suppressive activity, with both NO and PGE(2) levels in the culture supernatant rising with Ad cell concentration. OVA-p ulsed Ad cells (OVA-Ad cells) were found to stimulate IFN-gamma production, resulting in an elevation of the NO and PGE(2) levels in wells containing OVA-specific Th1 clones. No DNA synthesis by these clones was detected in t he absence of N-G-monomethyl-L-arginine and indomethacin, yet the prolifera tion of the clone was induced in the presence of these chemicals. As prolif eration is inhibited by NO and PGE(2) the Ad cells give the impression that they have no antigen-presenting function. This function is MHC-class-II-re stricted. If cells such as Ad cells did actually exist in the hepatic sinus oid, they could by their nature play a major role in inducing the early eme rging unresponsiveness of T cells in the liver which we reported in a previ ous paper. (C) 1999 Academic Press.