CXCR5+ T helper cells mediate protective immunity against tuberculosis
CXCR5+ T helper cells mediate protective immunity against tuberculosis
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DOI：
10.1172/jci65728
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发表时间：
2013-02-01
影响因子：
15.9
通讯作者：
Khaderl, Shabaana A.
中科院分区：
文献类型：
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作者：
Slight, Samantha R.;Rangel-Moreno, Javier;Khaderl, Shabaana A.
世界上三分之一的人口感染结核分枝杆菌(Mtb)。尽管大多数感染者仍然没有症状，但他们一生中有10%的风险发展为活动性结核病(TB)。因此，目前的挑战是确定免疫参数，以区分潜伏性结核病患者和活动性结核病患者。利用人和实验的结核分枝杆菌感染模型，我们证明了结核分枝杆菌感染的肺中存在含有CXCR5(+)T细胞的有组织的异位淋巴结构。此外，我们发现在实验性结核分枝杆菌感染模型中，异位淋巴结构中CXCR5(+)T细胞的存在与免疫控制有关。此外，在结核杆菌感染的小鼠模型中，我们发现活化的CD4(+)CXCR5(+)T细胞在结核杆菌感染的肺中积聚，并产生促炎细胞因子。缺乏CXCR5的小鼠由于肺实质内T细胞定位缺陷而增加了对结核病的易感性。我们证明，CXCR5在T细胞中的表达介导了T细胞在TB肉芽肿中的正确定位，促进了巨噬细胞的有效激活，保护了结核分枝杆菌感染，并促进了淋巴滤泡的形成。这些数据表明，CD4(+)CXCR5(+)T细胞在针对结核病的免疫反应中发挥了保护作用，并突出了它们在未来结核病疫苗设计和治疗中的潜在用途。
One third of the world's population is infected with Mycobacterium tuberculosis (Mtb). Although most infected people remain asymptomatic, they have a 10% lifetime risk of developing active tuberculosis (TB). Thus, the current challenge is to identify immune parameters that distinguish individuals with latent TB from those with active TB. Using human and experimental models of Mtb infection, we demonstrated that organized ectopic lymphoid structures containing CXCR5(+) T cells were present in Mtb-infected lungs. In addition, we found that in experimental Mtb infection models, the presence of CXCR5(+) T cells within ectopic lymphoid structures was associated with immune control. Furthermore, in a mouse model of Mtb infection, we showed that activated CD4(+)CXCR5(+) T cells accumulated in Mtb-infected lungs and produced proinflammatory cytokines. Mice deficient in Cxcr5 had increased susceptibility to TB due to defective T cell localization within the lung parenchyma. We demonstrated that CXCR5 expression in T cells mediated correct T cell localization within TB granulomas, promoted efficient macrophage activation, protected against Mtb infection, and facilitated lymphoid follicle formation. These data demonstrate that CD4(+)CXCR5(+) T cells play a protective role in the immune response against TB and highlight their potential use for future TB vaccine design and therapy.