Rojas R E, Balaji K N, Subramanian A, Boom W H
Department of Medicine, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4984, USA.
Infect Immun. 1999 Dec;67(12):6461-72. doi: 10.1128/IAI.67.12.6461-6472.1999.
Mycobacterium tuberculosis is the etiologic agent of human tuberculosis and is estimated to infect one-third of the world's population. Control of M. tuberculosis requires T cells and macrophages. T-cell function is modulated by the cytokine environment, which in mycobacterial infection is a balance of proinflammatory (interleukin-1 [IL-1], IL-6, IL-8, IL-12, and tumor necrosis factor alpha) and inhibitory (IL-10 and transforming growth factor beta [TGF-beta]) cytokines. IL-10 and TGF-beta are produced by M. tuberculosis-infected macrophages. The effect of IL-10 and TGF-beta on M. tuberculosis-reactive human CD4(+) and gammadelta T cells, the two major human T-cell subsets activated by M. tuberculosis, was investigated. Both IL-10 and TGF-beta inhibited proliferation and gamma interferon production by CD4(+) and gammadelta T cells. IL-10 was a more potent inhibitor than TGF-beta for both T-cell subsets. Combinations of IL-10 and TGF-beta did not result in additive or synergistic inhibition. IL-10 inhibited gammadelta and CD4(+) T cells directly and inhibited monocyte antigen-presenting cell (APC) function for CD4(+) T cells and, to a lesser extent, for gammadelta T cells. TGF-beta inhibited both CD4(+) and gammadelta T cells directly and had little effect on APC function for gammadelta and CD4(+) T cells. IL-10 down-regulated major histocompatibility complex (MHC) class I, MHC class II, CD40, B7-1, and B7-2 expression on M. tuberculosis-infected monocytes to a greater extent than TGF-beta. Neither cytokine affected the uptake of M. tuberculosis by monocytes. Thus, IL-10 and TGF-beta both inhibited CD4(+) and gammadelta T cells but differed in the mechanism used to inhibit T-cell responses to M. tuberculosis.
结核分枝杆菌是人类结核病的病原体，据估计全球三分之一的人口受到感染。控制结核分枝杆菌需要T细胞和巨噬细胞。T细胞功能受细胞因子环境调节，在分枝杆菌感染中，细胞因子环境是促炎细胞因子（白细胞介素-1 [IL-1]、IL-6、IL-8、IL-12和肿瘤坏死因子α）和抑制性细胞因子（IL-10和转化生长因子β [TGF-β]）的平衡。IL-10和TGF-β由感染结核分枝杆菌的巨噬细胞产生。研究了IL-10和TGF-β对结核分枝杆菌反应性人类CD4(+)和γδ T细胞（被结核分枝杆菌激活的两种主要人类T细胞亚群）的影响。IL-10和TGF-β均抑制CD4(+)和γδ T细胞的增殖和γ干扰素产生。对于这两种T细胞亚群，IL-10的抑制作用比TGF-β更强。IL-10和TGF-β联合使用未产生相加或协同抑制作用。IL-10直接抑制γδ和CD4(+) T细胞，并抑制单核细胞抗原呈递细胞（APC）对CD4(+) T细胞的功能，对γδ T细胞的抑制作用较小。TGF-β直接抑制CD4(+)和γδ T细胞，对γδ和CD4(+) T细胞的APC功能影响较小。与TGF-β相比，IL-10更能下调感染结核分枝杆菌的单核细胞上主要组织相容性复合体（MHC）I类、MHC II类、CD40、B7-1和B7-2的表达。两种细胞因子均不影响单核细胞对结核分枝杆菌的摄取。因此，IL-10和TGF-β均抑制CD4(+)和γδ T细胞，但在抑制T细胞对结核分枝杆菌反应的机制上有所不同。
