Modulation of Ia-like antigen expression and antigen-presenting activity of human monocytes by endotoxin and zymosan A.
The environmental agents E. coli endotoxin and zymosan A modulated antigen-specific T cell proliferation in vitro, assessed by 3H-TdR uptake. In the continual presence of these agents, human mononuclear leukocyte responses to the antigens tuberculin PPD, Candida albicans, and mumps were significantly reduced. Treatment of adherent cell-depleted T cells with the agents did not affect their subsequent reactivity to soluble antigens in the presence of normal M phi. However, cultures consisting of pretreated M phi, normal T cells, and soluble antigen gave responses that were only 7 to 38% of control values, indicating that the function of the antigen-presenting cell, not the T cell, was inhibited. This effect was observed only when treatment with endotoxin or zymosan A preceded antigen stimulation by at least 24 hr, suggesting that a gradual inhibition of antigen presentation had occurred. When various ratios of normal antigen-pulsed and agent-treated M phi were cultured with normal T cells, antigen-specific responses were not significantly different from control cultures; this indicated that M phi-mediated suppression was not involved. It did not appear that the inhibition was due to enhanced antigen degradation by the treated M phi because responses were not reconstituted in the presence of excess antigen. After endotoxin or zymosan A treatment of the M phi population the proportion of Ia+ cells was reduced significantly, and surface expression of Ia antigen correlated with the ability of the cell population to present antigens to immune T cells. This suggested that endotoxin and zymosan A induce a loss of surface Ia antigen on antigen-presenting cells that inhibits immune T cell activation.
D000818:Animals; D000941:Antigens; D000954:Antigens, Surface; D004731:Endotoxins / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology*; D011817:Rabbits; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D015054:Zymosan / Q000494:pharmacology*
D000941:Antigens; D000954:Antigens, Surface; D004731:Endotoxins; D000949:Histocompatibility Antigens Class II; D015054:Zymosan