title: Relationship between ineffective antigen presentation by murine alveolar macrophages and their immunosuppressive function.
abstract: Murine alveolar macrophages (AM) have been shown to be inefficient at providing accessory function for initiation of the in vitro plaque-forming cell (PFC) response. In the present study AM, which were obtained either from untreated mice (resident AM) or mice injected i.v. with BCG (activated AM) potently suppressed the PFC response of spleen cells from animals previously primed with sheep erythrocytes (SRBC). Addition of AM at a concentration of 10% with respect to spleen cells resulted in greater than 90% suppression of the PFC response. In order to determine if inefficient antigen presentation was associated with AM-mediated suppression, the role of IL-1 and Ia antigen was studied. Addition of exogenous recombinant IL-1 (rIL-1) stimulated the PFC response in control cultures, but had no effect on AM-mediated suppression. Resident AM could be activated with lipopolysaccharide or antigen to produce significant levels of IL-1. Membrane-bound IL-1, thought to be important in the presentation of particulate antigens, was detected on glutaraldehyde-fixed resident AM and was significantly elevated in BCG-activated macrophages. The frequency of cell surface Ia antigen expression was low in resident AM (4%), but could be increased (35%) after in vivo activation with BCG. Recombinant interferon-gamma (IFN-gamma), known to enhance expression of Ia antigen and production of IL-1, had no effect on AM-mediated suppression when used either to pretreat AM, when present during the entire period of culture, or when injected into mice before culture initiation. Treatment with IFN-gamma, however, resulted in a slight increase in the expression of Ia antigen. These results indicate that the immunosuppressive activity of AM is neither related to a defect in IL-1 production or expression nor to a deficiency in Ia antigen expression and therefore can not be explained by the inefficient antigen-presenting function of alveolar macrophages.
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002478:Cells, Cultured; D006462:Hemolytic Plaque Technique; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis; D011650:Pulmonary Alveoli / Q000166:cytology; D013154:Spleen / Q000276:immunology
chemical_list: D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007371:Interferon-gamma