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肠道和脾脏T细胞对肠道单核细胞增生李斯特菌感染的反应:应答性CD8 T淋巴细胞的不同库

Intestinal and splenic T cell responses to enteric Listeria monocytogenes infection: distinct repertoires of responding CD8 T lymphocytes.

作者信息

Huleatt J W, Pilip I, Kerksiek K, Pamer E G

机构信息

Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA.

出版信息

J Immunol. 2001 Mar 15;166(6):4065-73. doi: 10.4049/jimmunol.166.6.4065.

DOI:10.4049/jimmunol.166.6.4065
PMID:11238655
Abstract

Listeria monocytogenes is an intracellular bacterium that causes systemic infections after traversing the intestinal mucosa. Clearance of infection and long term protective immunity are mediated by L. monocytogenes-specific CD8 T lymphocytes. In this report, we characterize the murine CD8 T cell response in the lamina propria and intestinal epithelium after enteric L. monocytogenes infection. We find that the frequency of MHC class Ia-restricted, L. monocytogenes-specific T cells is approximately 4- to 5-fold greater in the lamina propria than in the spleen of mice after oral or i.v. infection. Although the kinetics of T cell expansion and contraction are similar in spleen, lamina propria, and intestinal epithelium, high frequencies of Ag-specific T cells are detected only in the lamina propria 1 mo after infection. In contrast to MHC class Ia-restricted T cells, the frequency of H2-M3-restricted, L. monocytogenes-specific T cells is decreased in the intestinal mucosa relative to that found in the spleen. In addition to this disparity, we find that MHC class Ia-restricted CD8 T cells specific for a dominant L. monocytogenes epitope have different TCR V beta repertoires in the spleen and intestinal mucosa of individual mice. These findings indicate that the intestinal mucosa is a depot where L. monocytogenes-specific effector CD8 T cells accumulate during and after infection irrespective of immunization route. Furthermore, our results demonstrate that CD8 T cell populations in these two sites, although overlapping in Ag specificity, are distinct in terms of their repertoire.

摘要

单核细胞增生李斯特菌是一种细胞内细菌,在穿过肠粘膜后会引发全身感染。感染的清除和长期保护性免疫由单核细胞增生李斯特菌特异性CD8 T淋巴细胞介导。在本报告中,我们描述了肠道感染单核细胞增生李斯特菌后,小鼠固有层和肠上皮中的CD8 T细胞反应。我们发现,口服或静脉注射感染后,小鼠固有层中MHC I类分子限制性、单核细胞增生李斯特菌特异性T细胞的频率比脾脏中的高约4至5倍。尽管T细胞扩增和收缩的动力学在脾脏、固有层和肠上皮中相似,但仅在感染后1个月的固有层中检测到高频率的抗原特异性T细胞。与MHC I类分子限制性T细胞相反,相对于脾脏中发现的频率,肠道粘膜中H2-M3限制性、单核细胞增生李斯特菌特异性T细胞的频率降低。除了这种差异外,我们发现,针对单核细胞增生李斯特菌优势表位的MHC I类分子限制性CD8 T细胞在个体小鼠的脾脏和肠道粘膜中具有不同的TCR Vβ库。这些发现表明,无论免疫途径如何,肠道粘膜都是感染期间和感染后单核细胞增生李斯特菌特异性效应CD8 T细胞积累的场所。此外,我们的结果表明,这两个部位的CD8 T细胞群体虽然在抗原特异性上有重叠,但在库方面是不同的。

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