Granulocyte-macrophage colony-stimulating factor-cultured bone marrow-derived macrophages reveal accessory cell function and synthesis of MHC class II determinants in the absence of external stimuli

Abstract

The antigen-mediated activation of a number of T cell clones by bone marrow (BM) cells cultivated in the presence of various colony-stimulating factor (CSF) preparations was investigated. BM macrophages (BMM phi) grown in L929 cell supernatant as a crude source of macrophage colony-stimulating factor (M-CSF) as well as BM cells propagated in the presence of recombinant M-CSF exhibited transient antigen presentation potential to some T cell clones, being maximal on day 7 and having declined to a low level by day 19 of in vitro culture. Treatment of these long-term-cultivated BMM phi populations with recombinant interferon-gamma (IFN-gamma) resulted in predominant antigen presentation capacity. In contrast, BM cells differentiated in the presence of recombinant granulocyte (G)M-CSF developed highly efficient accessory cell function to all T cell clones examined. This function became apparent earlier, was retained during the time period tested (up to day 19 of continuous culture) and did not require prior stimulation by IFN-gamma. The functionally competent cells were shown to belong to the monocyte/macrophage lineage. These findings are consistent with the demonstration of substantial levels of major histocompatibility complex (MHC) class II molecules synthesized by GM-CSF-cultured BM cells in the absence of exogenous IFN-gamma. In contrast, M-CSF grown BM cells synthesized only minute amounts of Ia antigens unless they were stimulated by IFN-gamma. Because GM-CSF-cultivated BM cells proved clearly superior to M-CSF-grown and IFN-gamma-activated BM cells with respect to antigen-presenting capacity but exhibited lower levels of MHC class II molecules, other properties acting in addition to surface Ia antigens might be responsible for their pronounced T cell accessory function.