Molecular Immunogenetics and Vaccine Research Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Eur J Immunol. 2011 Dec;41(12):3513-28. doi: 10.1002/eji.201141453.
Survival of antigen-specific CD8(+) T cells in peripheral lymphoid organs during viral infection is known to be dependent predominantly on IL-7 and IL-15. However, little is known about a possible influence of tissue environmental factors on this process. To address this question, we studied survival of memory antigen-specific CD8(+) T cells in the small intestine. Here, we show that 2 months after vaccinia virus infection, B8R(20-27) /H2-K(b) tetramer(+) CD8(+) T cells in the small intestinal intraepithelial (SI-IEL) layer are found in mice deficient in IL-15 expression. Moreover, SI-IEL and lamina propria lymphocytes do not express the receptor for IL-7 (IL-7Rα/CD127). In addition, after in vitro stimulation with B8R(20-27) peptide, SI-IEL cells do not produce high amounts of IFN-γ neither at 5 days nor at 2 months postinfection (p.i.). Importantly, the lack of IL-15 was found to shape the functional activity of antigen-specific CD8(+) T cells, by narrowing the CTL avidity repertoire. Taken together, these results reveal that survival factors, as well as the functional activity, of antigen-specific CD8(+) T cells in the SI-IEL compartments may markedly differ from their counterparts in peripheral lymphoid tissues.
在病毒感染期间,外周淋巴器官中抗原特异性 CD8(+) T 细胞的存活被认为主要依赖于 IL-7 和 IL-15。然而,对于组织环境因素对这一过程可能产生的影响,人们知之甚少。为了解决这个问题,我们研究了记忆性抗原特异性 CD8(+) T 细胞在小肠中的存活情况。在这里,我们发现,在接种牛痘病毒 2 个月后,IL-15 表达缺陷的小鼠小肠上皮内(SI-IEL)层中存在 B8R(20-27)/H2-K(b)四聚体(+) CD8(+) T 细胞。此外,SI-IEL 和固有层淋巴细胞不表达 IL-7 受体(IL-7Rα/CD127)。此外,在体外用 B8R(20-27) 肽刺激后,SI-IEL 细胞在感染后 5 天和 2 个月时均不产生大量 IFN-γ。重要的是,缺乏 IL-15 被发现会影响抗原特异性 CD8(+) T 细胞的功能活性,从而缩小 CTL 亲和力谱。总之,这些结果表明,抗原特异性 CD8(+) T 细胞在 SI-IEL 区的存活因子以及其功能活性可能与外周淋巴组织中的对应物明显不同。