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.
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.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D000941:Antigens; D001854:Bone Marrow Cells; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006825:Hybridomas / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
D000941:Antigens; D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor