Woodworth J S, Cohen S B, Moguche A O, Plumlee C R, Agger E M, Urdahl K B, Andersen P
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
Center for Infectious Disease Research, Seattle, Washington, USA.
Mucosal Immunol. 2017 Mar;10(2):555-564. doi: 10.1038/mi.2016.70. Epub 2016 Aug 24.
The capacity of CD4 T cells to protect against Mycobacterium tuberculosis (Mtb) is governed by their ability to localize to the lung site of infection. Subunit vaccine H56/CAF01, a liposome-adjuvanted fusion protein of Mtb antigens Ag85B, ESAT-6, and Rv2660, conferred durable protection and elicited polyfunctional CD4 T cells that preferentially localized to the lung parenchyma. These lung-resident T cells had reduced KLRG1 and increased CXCR3 expression, an intermediate state of Th1 differentiation that has been associated with Mtb protection. Importantly, KLGR1 CXCR3 cells were also enriched in the lung vasculature and peripheral circulation of vaccinated animals, but not controls. Moreover, S1P1R blockade rapidly cleared this population from the blood and adoptive transfer of T cells recovered from the vasculature of vaccinated, but not control, mice efficiently trafficked into the Mtb-infected lung parenchyma. Thus, durable immunity elicited by H56/CAF01 vaccination is associated with the maintenance of circulating CD4 T cells that selectively home to the lung parenchyma.
CD4 T细胞抵御结核分枝杆菌（Mtb）感染的能力取决于其定位于肺部感染部位的能力。亚单位疫苗H56/CAF01是一种脂质体佐剂化的Mtb抗原Ag85B、ESAT-6和Rv2660的融合蛋白，可提供持久的保护，并诱导优先定位于肺实质的多功能CD4 T细胞。这些驻留在肺部的T细胞KLRG1表达降低，CXCR3表达增加，这是与Mtb保护相关的Th1分化中间状态。重要的是，在接种疫苗的动物而非对照动物的肺血管和外周循环中，KLGR1 CXCR3细胞也有所富集。此外，S1P1R阻断可迅速从血液中清除这一细胞群，从接种疫苗而非对照小鼠的血管中回收的T细胞进行过继转移后，能够有效地迁移到感染Mtb的肺实质中。因此，H56/CAF01疫苗接种所引发的持久免疫与维持选择性归巢至肺实质的循环CD4 T细胞有关。
