Zhang M, Gong J, Presky D H, Xue W, Barnes P F
Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler 75710, USA.
J Immunol. 1999 Feb 15;162(4):2441-7.
To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma production. In combination with prior studies showing increased production of TGF-beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis. Our findings provide evidence that IL-12R expression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a protective Th1 response.
为了确定结核病中的Th1反应是否与IL-12R表达相关，我们检测了结核病患者和健康结核菌素反应者中IL-12Rβ1和IL-12Rβ2亚基的表达以及IL-12Rβ2 mRNA的表达。在结核病患者中，结核分枝杆菌刺激的外周血单个核细胞（PBMC）产生的IFN-γ减少，表达IL-12Rβ1和IL-12Rβ2的T细胞百分比显著降低，并且IL-12Rβ2 mRNA表达也明显降低。相比之下，在结核病患者疾病部位的胸腔积液和淋巴结中，IFN-γ产生增加，IL-12Rβ2 mRNA表达也增加。在结核病患者的结核分枝杆菌刺激的外周血T细胞中，抗IL-10和抗TGF-β增强了IL-12Rβ1和IL-12Rβ2的表达以及IFN-γ的产生。在健康结核菌素反应者的结核分枝杆菌刺激的外周血T细胞中，重组IL-10和TGF-β降低了IL-12Rβ1和IL-12Rβ2的表达以及IFN-γ的产生。结合先前的研究表明结核病患者血液单核细胞中TGF-β产生增加，这表明TGF-β产生增加是降低结核病中IL-12Rβ1和IL-12Rβ2表达的潜在异常。我们的研究结果提供了证据，表明IL-12R表达与人类结核病中的IFN-γ产生密切相关，并且IL-12Rβ1和IL-12Rβ2的表达可能在介导保护性Th1反应中起核心作用。
