NIH/NIAID Laboratory of Parasitic Diseases, Bethesda, Maryland, United States of America.
PLoS Pathog. 2011 May;7(5):e1002052. doi: 10.1371/journal.ppat.1002052. Epub 2011 May 19.
CD4 T cell deficiency or defective IFNγ signaling render humans and mice highly susceptible to Mycobacterium tuberculosis (Mtb) infection. The prevailing model is that Th1 CD4 T cells produce IFNγ to activate bactericidal effector mechanisms of infected macrophages. Here we test this model by directly interrogating the effector functions of Th1 CD4 T cells required to control Mtb in vivo. While Th1 CD4 T cells specific for the Mtb antigen ESAT-6 restrict in vivo Mtb growth, this inhibition is independent of IFNγ or TNF and does not require the perforin or FAS effector pathways. Adoptive transfer of Th17 CD4 T cells specific for ESAT-6 partially inhibited Mtb growth while Th2 CD4 T cells were largely ineffective. These results imply a previously unrecognized IFNγ/TNF independent pathway that efficiently controls Mtb and suggest that optimization of this alternative effector function may provide new therapeutic avenues to combat Mtb through vaccination.
CD4 T 细胞缺陷或 IFNγ 信号转导缺陷使人类和小鼠极易受到结核分枝杆菌（Mtb）感染。目前的模型是，Th1 CD4 T 细胞产生 IFNγ 来激活受感染的巨噬细胞的杀菌效应机制。在这里，我们通过直接研究体内控制 Mtb 所需的 Th1 CD4 T 细胞的效应功能来检验该模型。虽然针对 Mtb 抗原 ESAT-6 的 Th1 CD4 T 细胞特异性限制了体内 Mtb 的生长，但这种抑制作用不依赖于 IFNγ 或 TNF，也不依赖于穿孔素或 Fas 效应途径。针对 ESAT-6 的 Th17 CD4 T 细胞的过继转移部分抑制了 Mtb 的生长，而 Th2 CD4 T 细胞则基本无效。这些结果表明存在一种以前未被认识的 IFNγ/TNF 非依赖性途径，该途径能有效地控制 Mtb，并提示通过疫苗接种优化这种替代效应功能可能为对抗 Mtb 提供新的治疗途径。
