Suppressed induction of mycobacterial antigen-specific Th1-type CD4+Tcells in the lung after pulmonary mycobacterial infection
Suppressed induction of mycobacterial antigen-specific Th1-type CD4+Tcells in the lung after pulmonary mycobacterial infection
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肺部分枝杆菌感染后肺部分枝杆菌抗原特异性 Th1 型 CD4 T 细胞的诱导受到抑制
DOI：
10.1093/intimm/dxq010
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
G
中科院分区：
文献类型：
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作者：
Yahagi;A.;Umemura;M.;Tamura;T.;Kariyone;A.;Begum;M. D.;Kawakami;K.;Okamoto;Y.;Hamada;S.;Oshiro;K.;Kohama;H.;Arakawa;T.;Ohara;N.;Takatsu;K.;Matsuzaki;G
尽管Th1型免疫反应在预防分枝杆菌感染中的重要性已被公认，但其在结核分枝杆菌(Mtb)感染肺中的调节机制尚未得到很好的描述。为了解决这个问题，我们分析了P25TCR转基因(TG)小鼠在分枝杆菌感染后诱导分枝杆菌抗原特异性CD_4+Th1T细胞的动力学，这些小鼠表达了分枝杆菌Ag85B特异性MHC II类抗体限制性CD_4+T细胞克隆的TCRα和β链。为了提供正常的调节性T细胞库，我们在感染前将正常的脾T细胞转移到P25TCR-TG小鼠体内。大剂量Mtb或卡介苗(BCG)皮下感染在一周内可诱导P25 TCR-TGCD4+Th1细胞。相比之下，大剂量的结核分枝杆菌或卡介苗肺内感染在感染早期未能诱导P25 TCR-TG CD4+Th1细胞。此外，低剂量结核分枝杆菌肺内感染在第21天在纵隔淋巴结中诱导了P25TCR-TGCD4+Th1细胞，但在肺中未见。IL-10可部分抑制小鼠肺内Th1型细胞的诱导，这是因为抗IL-10抗体可使结核分枝杆菌感染后第21天小鼠肺内P25TCR-TGCD+Th1细胞数量增加，而肺内另一种重要的抑制性细胞因子转化生长因子β的中和对Th1型细胞的诱导无影响。我们的数据表明，在分枝杆菌感染的肺中，IL-10部分抑制了抗分枝杆菌CD4+Th1细胞的诱导。
Although the importance of Th1-type immune response in protection against mycobacterial infection is well recognized, its regulatory mechanism in theMycobacterium tuberculosis(Mtb)-infected lung is not well characterized. To address this issue, we analyzed kinetics of induction of mycobacterial antigen-specific CD4+Th1 T cells after mycobacterial infection in P25 TCR-transgenic (Tg) mice which express TCR α and β chains from a mycobacterial Ag85B-specific MHC class II Ab-restricted CD4+T-cell clone. To supply normal regulatory T-cell repertoire, we transferred normal spleen T cells into the P25 TCR-Tg mice before infection. High dose subcutaneous infection with Mtb orMycobacterium bovisbacillus Calmette–Guérin (BCG) induced P25 TCR-Tg CD4+Th1 cells within a week. In contrast, high-dose Mtb or BCG infection into the lung failed to induce P25 TCR-Tg CD4+Th1 cells at the early stage of the infection. Furthermore, low-dose Mtb infection into the lung induced P25 TCR-Tg CD4+Th1 cells on day 21 in the mediastinal lymph node but not in the lung. IL-10 was partially involved in the suppression of Th1 induction in the lung because pretreatment of mice with anti-IL-10 antibody resulted in increase of P25 TCR-Tg CD4+Th1 cells in the Mtb-infected lung on day 21 of the infection, whereas neutralization of transforming growth factor-β, another important suppressive cytokine in the lung, showed no effects on the Th1 induction. Our data suggest that induction of anti-mycobacterial CD4+Th1 cells is suppressed in the mycobacteria-infected lung partially by IL-10.