Belyakov Igor M, Isakov Dmitry, Zhu Qing, Dzutsev Amiran, Berzofsky Jay A
Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2007 Jun 1;178(11):7211-21. doi: 10.4049/jimmunol.178.11.7211.
The presence of high-avidity CTLs in the right compartment can greatly affect clearance of a virus infection (for example, AIDS viral infection of and dissemination from mucosa). Comparing mucosal vs systemic immunization, we observed a novel compartmentalization of CTL avidity and proportion of functionally active Ag-specific CD8(+) T cells to tissues proximal to sites of immunization. Whereas both s.c. and intrarectal routes of immunization induced tetramer(+) cells in the spleen and gut, the mucosal vaccine induced a higher percentage of functioning IFN-gamma(+) Ag-specific CD8(+) T cells in the gut mucosa in mice. Translating to the CD8(+) CTL avidity distribution in rhesus macaques, intrarectal vaccination induced more high-avidity mucosal CTL than s.c. vaccination and protection of mucosal CD4(+) T cells from AIDS viral depletion, whereas systemic immunization induced higher avidity IFN-gamma-secreting cells in the draining lymph nodes but no protection of mucosal CD4(+) T cells, after mucosal challenge with pathogenic simian/human immunodeficiency virus. Mucosal CD4(+) T cell loss is an early critical step in AIDS pathogenesis. The preservation of CD4(+) T cells in colonic lamina propria and the reduction of virus in the intestine correlated better with high-avidity mucosal CTL induced by the mucosal AIDS vaccine. This preferential localization of high-avidity CTL may explain previous differences in vaccination results and may guide future vaccination strategy.
右侧腔室中高亲和力细胞毒性T淋巴细胞（CTL）的存在会极大地影响病毒感染的清除（例如，艾滋病病毒在黏膜处的感染及传播）。比较黏膜免疫和全身免疫，我们观察到CTL亲和力以及功能性活性抗原特异性CD8(+) T细胞在免疫接种部位近端组织中的比例呈现出一种新的分区现象。虽然皮下和直肠内免疫途径均可在脾脏和肠道中诱导产生四聚体(+)细胞，但黏膜疫苗在小鼠肠道黏膜中诱导产生的功能性γ干扰素(+)抗原特异性CD8(+) T细胞比例更高。在恒河猴中，直肠内接种诱导产生的黏膜CTL亲和力高于皮下接种，且能保护黏膜CD4(+) T细胞免受艾滋病病毒耗竭，而全身免疫在致病性猿猴/人类免疫缺陷病毒黏膜攻击后，在引流淋巴结中诱导产生的分泌γ干扰素的细胞亲和力更高，但不能保护黏膜CD4(+) T细胞。黏膜CD4(+) T细胞的丧失是艾滋病发病机制中的一个早期关键步骤。结肠固有层中CD4(+) T细胞的保留以及肠道中病毒的减少与黏膜艾滋病疫苗诱导产生的高亲和力黏膜CTL相关性更好。高亲和力CTL的这种优先定位可能解释了先前疫苗接种结果的差异，并可能指导未来的疫苗接种策略。
