GAMMA DELTA T CELLS AND TUBERCULOSIS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在人类感染过程中，抗原特异性T细胞在组织/器官粘膜界面的免疫分布和定位尚不清楚。在这项研究中，我们利用结核分枝杆菌感染的猕猴模型来评估磷酸抗原特异性的VGamma2Vdelta2T细胞的组织分布、解剖定位以及与重症肺结核进展过程中淋巴和非淋巴器官/组织中是否存在结核病(TB)病变的相关性。结核分枝杆菌感染的进展导致VGamma2Vdelta2T细胞的分布模式多样化，这些细胞显著聚集在肺、支气管淋巴结、脾和远处的非淋巴器官，而不是在血液中。组织中VGamma2Vdelta2T细胞数量的增加与结核分枝杆菌感染有关，但与结核病变的严重程度无关。在有明显结核病损的肺部，结核肉芽肿内可见VGamma2Vdelta2T细胞。在胸外器官中，VGamma2Vdelta2T细胞定位于非淋巴组织的间质内，尽管未发现结核病变，但间质内仍有定位。最后，组织中聚集的VGamma2Vdelta2T细胞似乎具有细胞因子产生功能，因为在肉芽肿内存在的Gamma Delta T细胞中可检测到颗粒酶B。因此，克隆扩增的VGamma2Vdelta2T细胞似乎经历了跨内皮细胞迁移、间质定位和肉芽肿浸润，作为对结核分枝杆菌感染的免疫反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Little is known about the immune distribution and localization of antigen-specific T cells in mucosal interfaces of tissues/organs during infection of humans. In this study, we made use of a macaque model of Mycobacterium tuberculosis infection to assess phosphoantigen-specific Vgamma2Vdelta2 T cells regarding their tissue distribution, anatomical localization, and correlation with the presence or absence of tuberculosis (TB) lesions in lymphoid and nonlymphoid organs/tissues in the progression of severe pulmonary TB. Progression of pulmonary M. tuberculosis infection generated diverse distribution patterns of Vgamma 2Vdelta 2 T cells, with remarkable accumulation of these cells in lungs, bronchial lymph nodes, spleens, and remote nonlymphoid organs but not in blood. Increased numbers of Vgamma 2Vdelta 2 T cells in tissues were associated with M. tuberculosis infection but were independent of the severity of TB lesions. In lungs with apparent TB lesions, Vgamma 2Vdelta 2 T cells were present within TB granulomas. In extrathoracic organs, Vgamma 2Vdelta 2 T cells were localized in the interstitial compartment of nonlymphoid tissues, and the interstitial localization was present despite the absence of detectable TB lesions. Finally, Vgamma 2Vdelta 2 T cells accumulated in tissues appeared to possess cytokine production function, since granzyme B was detectable in the gamma delta T cells present within granulomas. Thus, clonally expanded Vgamma 2Vdelta 2 T cells appeared to undergo trans-endothelial migration, interstitial localization, and granuloma infiltration as immune responses to M. tuberculosis infection.