The accessory cell function of human alveolar macrophages in specific T cell proliferation.
The capacity of alveolar macrophages to support mitogen- and antigen-induced proliferation of autologous, monocyte-depleted T cells in normal, nonsmoking volunteers was studied. Purified T cells failed to proliferate in response to mitogen or antigen, whereas co-culture with peripheral blood monocytes restored responsiveness. Alveolar macrophages (AM) reconstituted the response of T cells to mitogen, indicating that AM can deliver a second proliferative signal. AM, however, were markedly inferior to monocytes in supporting antigen-induced proliferation. Thus, in 19 normal volunteers, the mean response of immune T cells to diphtheria toxoid in cultures reconstituted with normal AM was only 25% of the proliferative response to diphtheria in cultures with monocytes. Although four volunteers demonstrated antigen-presenting function equivalent to monocytes, in the remaining 15 antigen-presenting ability of AM was less than 15% that of monocytes. The difference in antigen-presenting function between AM and monocytes was not due to a difference in their display of HLA-D/DR determinants because 80% of AM were HLA-DR positive. The role of suppression in the diminished antigen-presenting function of AM was assessed in 12 volunteers utilizing mixing experiments. Eight volunteers demonstrated suppressor AM but four did not, suggesting that AM from at least some normal individuals have a faulty antigen-processing mechanism. Taken together, these studies demonstrate that AM may play three different roles in modulating T lymphocyte responses, i.e., they may present antigen, they may suppress normal responses, or they may remain immunologically inert. The factors that determine which function is expressed in vivo may determine the pulmonary response to inhaled antigen.
D000328:Adult; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D004285:Dogs; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000942:Antigens, Bacterial; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D003208:Concanavalin A