Roles of type II alveolar epithelial cells in T cell-dependent immune response in Mycobacterium tuberculosis infection

我们先前的研究表明，当小鼠受到分枝杆菌经气管内途径的攻击时，结核分枝杆菌(MTB)和禽分枝杆菌复合体(MAC)都会入侵肺泡II型上皮细胞。此外，结核分枝杆菌或肺炎衣原体感染的A-549人肺泡II型上皮细胞(A-549细胞)释放体液因子(肿瘤坏死因子-α和粒-巨噬细胞集落刺激因子)，从而增加巨噬细胞的抗分支杆菌活性(MφS)。在这项研究中，获得了以下发现。(1)抗肿瘤坏死因子-α和抗GM-CSF抗体可减弱A-549细胞对巨噬细胞内结核分枝杆菌和巨噬细胞生长的抑制作用，提示这两种细胞因子在A-549细胞介导的M-φ抗分枝杆菌活性增强中起重要作用。(2)在MTB感染的A-549细胞上加入人外周血单个核细胞(PBMC)，检测ConA或PPD诱导的T细胞有丝分裂，发现有A-549细胞的T细胞有丝分裂抑制作用明显高于无A-549细胞的T细胞有丝分裂抑制。在未感染MTB的A-549细胞中也观察到了这种抑制作用。当使用双室系统防止PBMC与A-549细胞接触时，也得到了类似的结果。因此，认为A-549细胞对PBMC有丝分裂的抑制作用依赖于A-549细胞释放的一些未知的体液T细胞抑制因子。

Our previous study revealed that both Mycobacterium tuberculosis (MTB) and M.avium complex (MAC) organisms invade type II alveolar epithelial cells in the lungs when mice are subjected to mycobacterial challenge via the intracheal route. In addition, MTB- or MAC-infected A-549 human type II alveolar epithelial cells (A-549 cells) release humoral factors (TNF-α and GM-CSF), thereby increasing antimycobacterial activity of macrophages(Mφs). In this study, the following findings have been obtained. (1) Anti-TNF-α and anti-GM-CSF antibodies attenuated A-549 cell-dependent inhibition of the intramacrophage growth of MTB and MAC, indicating crucial roles of these cytokines in A-549 cell-mediated potentiation of Mφ antimycobacterial activity. (2) When human peripheral blood mononuclear cells (PBMC) were added onto MTB-infected A-549 cells and Con A- or PPD-induced T cell mitogenesis was examined, T cell mitogenosis in the presence of A-549 cells was inhibited more profoundly than cases without A-549 cells. Such an inhibitory effect was also observed for A-549 cells without MTB infection. When a dual chamber system was used to prevent the cell contact between PBMC and A-549 cells, similar results were also obtained. Therefore, it is thought that the observed inhibition of PBMC mitogenesis due to A-549 cells is dependent upon some unknown humoral T cell-inhibitory factors released from A-549 cells.