Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, Victoria, Australia.
Mucosal Immunol. 2018 May;11(3):994-1007. doi: 10.1038/mi.2017.89. Epub 2017 Oct 25.
Tissue-resident memory (T) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 T cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 T cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 T cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 T cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 T cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.
组织驻留记忆 (T) CD8 T 细胞会在一系列非淋巴组织黏膜中进行检测，从而在病毒感染进入门户处迅速介导清除作用。在宫颈阴道黏膜中建立 CD8 T 细胞的疫苗有望对性传播的 HIV 产生有效的免疫。我们证明，使用鼻内和阴道黏膜联合免疫重组流感-HIV 载体，可以在小鼠阴道黏膜中建立 HIV 特异性 CD8 T 细胞。通过原位四聚体免疫荧光显微镜，我们发现这种黏膜给予的初始-加强免疫接种也导致 CD8 T 细胞在阴道上皮前区的持久定植，而不是在阴道黏膜下层。在阴道黏膜中识别到同源抗原后，这些 HIV 特异性 CD8 T 细胞迅速启动了广泛的组织免疫状态。HIV 特异性 CD8 T 细胞的激活导致内皮血管地址素表达上调，并在阴道黏膜中大量招募适应性和先天免疫细胞。这些发现表明，HIV 特异性 CD8 T 细胞群体在阴道中的上皮定位及其快速激活免疫系统两个分支的能力，可能会显著增强针对阴道 HIV 感染的一线防御。
