Department of Microbiology and Immunology, University of Melbourne, Melbourne 3010, Australia.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):7037-42. doi: 10.1073/pnas.1202288109. Epub 2012 Apr 16.
Although circulating memory T cells provide enhanced protection against pathogen challenge, they often fail to do so if infection is localized to peripheral or extralymphoid compartments. In those cases, it is T cells already resident at the site of virus challenge that offer superior immune protection. These tissue-resident memory T (T(RM)) cells are identified by their expression of the α-chain from the integrin α(E)(CD103)β(7), and can exist in disequilibrium with the blood, remaining in the local environment long after peripheral infections subside. In this study, we demonstrate that long-lived intraepithelial CD103(+)CD8(+) T(RM) cells can be generated in the absence of in situ antigen recognition. Local inflammation in skin and mucosa alone resulted in enhanced recruitment of effector populations and their conversion to the T(RM) phenotype. The CD8(+) T(RM) cells lodged in these barrier tissues provided long-lived protection against local challenge with herpes simplex virus in skin and vagina challenge models, and were clearly superior to the circulating memory T-cell cohort. The results demonstrate that peripheral T(RM) cells can be generated and survive in the absence of local antigen presentation and provide a powerful means of achieving immune protection against peripheral infection.
尽管循环记忆 T 细胞提供了针对病原体挑战的增强保护，但如果感染局限于外周或淋巴外器官，它们通常无法提供这种保护。在这些情况下，已经存在于病毒攻击部位的 T 细胞提供了更好的免疫保护。这些组织驻留记忆 T（T(RM)) 细胞通过其整合素 α(E)(CD103)β(7)的 α 链的表达来识别，并且可以与血液处于不平衡状态，在外周感染消退后很长时间仍留在局部环境中。在这项研究中，我们证明了在不存在原位抗原识别的情况下可以产生长寿命的上皮内 CD103(+)CD8(+)T(RM)细胞。皮肤和粘膜的局部炎症单独导致效应群体的增强募集及其向 T(RM)表型的转化。驻留在这些屏障组织中的 CD8(+)T(RM)细胞为皮肤和阴道挑战模型中的单纯疱疹病毒局部攻击提供了长期的保护，并且明显优于循环记忆 T 细胞群。结果表明，外周 T(RM)细胞可以在没有局部抗原呈递的情况下产生和存活，并为实现针对外周感染的免疫保护提供了一种有力手段。
