Department of Microbiology and Immunology, Center for Primate Biomedical Research, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
J Immunol. 2012 May 1;188(9):4278-88. doi: 10.4049/jimmunol.1101291. Epub 2012 Apr 2.
The possibility that simultaneous expansion of T regulatory cells (Treg) and T effector cells early postinfection can confer some immunological benefits has not been studied. In this study, we tested the hypothesis that early, simultaneous cytokine expansion of Treg and T effector cells in a tissue infection site can allow these T cell populations to act in concert to control tissue inflammation/damage while containing infection. IL-2 treatments early after Mycobacterium tuberculosis infection of macaques induced simultaneous expansion of CD4(+)CD25(+)Foxp3(+) Treg, CD8(+)CD25(+)Foxp3(+) T cells, and CD4(+) T effector/CD8(+) T effector/Vγ2Vδ2 T effector populations producing anti-M. tuberculosis cytokines IFN-γ and perforin, and conferred resistance to severe TB inflammation and lesions. IL-2-expanded Foxp3(+) Treg readily accumulated in pulmonary compartment, but despite this, rapid pulmonary trafficking/accumulation of IL-2-activated T effector populations still occurred. Such simultaneous recruitments of IL-2-expanded Treg and T effector populations to pulmonary compartment during M. tuberculosis infection correlated with IL-2-induced resistance to TB lesions without causing Treg-associated increases in M. tuberculosis burdens. In vivo depletion of IL-2-expanded CD4(+)Foxp3(+) Treg and CD4(+) T effectors during IL-2 treatment of M. tuberculosis-infected macaques significantly reduced IL-2-induced resistance to TB lesions, suggesting that IL-2-expanded CD4(+) T effector cells and Treg contributed to anti-TB immunity. Thus, IL-2 can simultaneously activate and expand T effector cells and Foxp3(+) Treg populations and confer resistance to severe TB without enhancing M. tuberculosis infection.
在感染后早期同时扩增调节性 T 细胞 (Treg) 和效应 T 细胞是否能带来一些免疫益处尚未得到研究。在本研究中，我们检验了一个假说，即在组织感染部位早期同时扩增 Treg 和效应 T 细胞的细胞因子可以使这些 T 细胞群协同作用，在控制组织炎症/损伤的同时控制感染。在猕猴感染结核分枝杆菌后早期给予白细胞介素-2 (IL-2) 治疗，诱导了 CD4+CD25+Foxp3+Treg、CD8+CD25+Foxp3+T 细胞和 CD4+T 效应细胞/CD8+T 效应细胞/Vγ2Vδ2T 效应细胞的同时扩增，这些细胞产生抗结核分枝杆菌细胞因子 IFN-γ和穿孔素，并赋予对严重结核病炎症和病变的抵抗力。IL-2 扩增的 Foxp3+Treg 容易在肺区积聚，但尽管如此，IL-2 激活的效应 T 细胞群仍迅速向肺部迁移/积聚。在结核分枝杆菌感染期间，这种同时向肺部募集 IL-2 扩增的 Treg 和效应 T 细胞群与 IL-2 诱导的对结核病病变的抵抗力相关，而不会导致 Treg 相关的结核分枝杆菌负荷增加。在结核分枝杆菌感染的猕猴中，在 IL-2 治疗期间体内耗竭 IL-2 扩增的 CD4+Foxp3+Treg 和 CD4+T 效应细胞显著降低了 IL-2 诱导的对结核病病变的抵抗力，这表明 IL-2 扩增的 CD4+T 效应细胞和 Treg 有助于抗结核免疫。因此，IL-2 可以同时激活和扩增效应 T 细胞和 Foxp3+Treg 群，并在不增强结核分枝杆菌感染的情况下赋予对严重结核病的抵抗力。
