Tsuyuguchi I, Kawasumi H, Takashima T, Tsuyuguchi T, Kishimoto S
Osaka Prefectural Habikino Hospital, Japan.
Infect Immun. 1990 May;58(5):1369-78. doi: 10.1128/iai.58.5.1369-1378.1990.
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.
热灭活的鸟分枝杆菌-胞内分枝杆菌复合体(MAC)及其脂质成分损害了人外周血单核细胞在体外对刀豆球蛋白A(ConA)、结核菌素纯蛋白衍生物(PPD)以及在较小程度上对植物血凝素刺激产生增殖反应的能力。MAC的抑制作用不取决于供体先前是否接触过MAC或其他分枝杆菌,并且在结核菌素阴性和阳性受试者的淋巴细胞中均会出现。这种抑制并非由于MAC的毒性。MAC的抑制作用不受吲哚美辛的阻断。贴壁细胞清除和T细胞混合实验表明,单核细胞而非T细胞是观察到的免疫抑制的主要促成因素。然而,MAC处理并未抑制单核细胞产生白细胞介素-1或其HLA-DR(Ia抗原)的表达。另一方面,用MAC或MAC衍生的脂质处理单核细胞会导致白细胞功能相关分子-1成员CD11b和LeuM3(CD14)分子显著减少。抗CD18(白细胞功能相关分子-1家族的β链)单克隆抗体对ConA和PPD诱导的而非植物血凝素诱导的体外淋巴细胞增殖有抑制作用。我们认为,MAC和MAC衍生的脂质通过阻断单核细胞表面可能参与非特异性单核细胞-T细胞相互作用的辅助分子的表达,而不是通过抑制单核细胞Ia抗原表达或单核细胞产生白细胞介素-1,来抑制ConA和PPD诱导的T细胞增殖。