Henao-Tamayo Marcela I, Obregón-Henao Andres, Arnett Kimberly, Shanley Crystal A, Podell Brendan, Orme Ian M, Ordway Diane J
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins CO, USA
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins CO, USA.
J Leukoc Biol. 2016 Apr;99(4):605-17. doi: 10.1189/jlb.4A0614-308RR. Epub 2015 Nov 20.
Increasing information has shown that many newly emerging strains of Mycobacterium tuberculosis, including the highly prevalent and troublesome Beijing family of strains, can potently induce the emergence of Foxp3(+)CD4 Tregs Although the significance of this is still not fully understood, we have previously provided evidence that the emergence of this population can significantly ablate the protective effect of BCG vaccination, causing progressive fatal disease in the mouse model. However, whether the purpose of this response is to control inflammation or to directly dampen the acquired immune response is still unclear. In the present study, we have shown, using both cell depletion and adoptive transfer strategies, that Tregs can have either properties. Cell depletion resulted in a rapid, but transient, decrease in the lung bacterial load, suggesting release or temporary re-expansion of effector immunity. Transfer of Tregs into Rag2(-/-)or marked congenic mice worsened the disease course and depressed cellular influx of effector T cells into the lungs. Tregs from infected donors seemed to preferentially depress the inflammatory response and granulocytic influx. In contrast, those from BCG-vaccinated and then challenged donors seemed more focused on depression of acquired immunity. These qualitative differences might be related to increasing knowledge reflecting the plasticity of the Treg response.
越来越多的信息表明，许多新出现的结核分枝杆菌菌株，包括高度流行且棘手的北京家族菌株，能够有力地诱导Foxp3(+)CD4调节性T细胞的出现。尽管其意义仍未完全明确，但我们之前已提供证据表明，这一细胞群体的出现能够显著消除卡介苗接种的保护作用，在小鼠模型中导致进行性致死性疾病。然而，这种反应的目的是控制炎症还是直接抑制获得性免疫反应仍不清楚。在本研究中，我们通过细胞清除和过继转移策略均表明，调节性T细胞可能具有这两种特性。细胞清除导致肺部细菌载量迅速但短暂地下降，提示效应性免疫的释放或暂时重新扩增。将调节性T细胞转移至Rag2(-/-)或标记的同基因小鼠中会使疾病进程恶化，并抑制效应性T细胞向肺部的细胞内流。来自感染供体的调节性T细胞似乎优先抑制炎症反应和粒细胞内流。相比之下，来自卡介苗接种后再受攻击供体的调节性T细胞似乎更侧重于抑制获得性免疫。这些质性差异可能与反映调节性T细胞反应可塑性的认识增加有关。
