Mycobacterium avium-Mycobacterium intracellular complex-induced suppression of T-cell proliferation in vitro by regulation of monocyte accessory cell activity.
Heat-killed whole Mycobacterium avium-Mycobacterium intracellulare complex (MAC) and its lipid component impaired the capacity of human peripheral blood mononuclear cells to proliferate in vitro in response to concanavalin A (ConA), purified protein derivative of tuberculin (PPD), and to a lesser degree, phytohemagglutinin stimulation. Inhibition by MAC was not contingent upon prior exposure of the donor to MAC or other mycobacteria and occurred with lymphocytes from tuberculin-negative as well as -positive subjects. The suppression was not due to the toxicity of MAC. The suppression by MAC was not blocked by indomethacin. Adherent cell depletion and cell mixing experiments with T cells indicated that monocytes and not T cells were a major contributor to the immunosuppression observed. However, neither interleukin-1 production nor the expression of HLA-DR (Ia antigen) by monocytes was suppressed by MAC treatment. On the other hand, treatment of monocytes with MAC or MAC-derived lipid resulted in significant decreases in CD11b, a member of the leukocyte function-associated molecule-1 and LeuM3 (CD14) molecule. Anti-CD18 (beta-chain of the leukocyte function-associated molecule-1 family) monoclonal antibody had suppressive effects on ConA- and PPD- but not phytohemagglutinin-induced in vitro lymphocyte blastogenesis. We suggest that MAC and MAC-derived lipid suppress the ConA- and PPD-induced T-cell proliferations by blocking the expression of accessory molecules on the surfaces of monocytes which might be involved in nonspecific monocyte-T-cell interactions and not by inhibiting either monocyte Ia antigen expression or interleukin-1 production by monocytes.
Osaka Prefectural Habikino Hospital, Japan.
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I
Tsuyuguchi
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H
Kawasumi
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T
Takashima
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T
Tsuyuguchi
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S
Kishimoto
D000938:Antigen-Presenting Cells / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D018821:CD18 Antigens; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008055:Lipids / Q000276:immunology; D018950:Lipopolysaccharide Receptors; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000502:physiology*; D015269:Mycobacterium avium Complex / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014373:Tuberculin / Q000276:immunology
D015214:Antigens, Differentiation, Myelomonocytic; D018821:CD18 Antigens; D006684:HLA-DR Antigens; D008055:Lipids; D018950:Lipopolysaccharide Receptors; D010835:Phytohemagglutinins; D016028:Receptors, Leukocyte-Adhesion; D014373:Tuberculin; D003208:Concanavalin A; D007213:Indomethacin