Pope C, Kim S K, Marzo A, Masopust D, Williams K, Jiang J, Shen H, Lefrançois L
Division of Rheumatic Diseases, University of Connecticut Health Center, Farmington, CT 06030, USA.
J Immunol. 2001 Mar 1;166(5):3402-9. doi: 10.4049/jimmunol.166.5.3402.
The intestinal mucosal CD8 T cell response to infection with Listeria monocytogenes was measured using MHC class I tetramers and was compared with the response in peripheral blood, secondary lymphoid tissue, and liver. To assess the vaccination potential of Listeria and to analyze responses in C57BL/6 mouse strains, a recombinant Listeria expressing OVA (rLM-ova) was generated. The response peaked at 9 days postinfection with a much larger fraction of the intestinal mucosa and liver CD8 T cell pool OVA specific, as compared with the spleen. However, these differences were not linked to bacterial titers in each site. The higher responses in lamina propria and liver resulted in a larger CD8 memory population in these tissues. Furthermore, the level of memory induced was dependent on infectious dose and inversely correlated with the magnitude of the recall response after oral challenge. Recall responses in the tissues were most robust in the lamina propria and liver, and reactivated Ag-specific T cells produced IFN-gamma. Infection of CD40- or MHC class II-deficient mice induced poor CD8 T cell responses in the intestinal mucosa, but only partially reduced responses in the spleen and liver. Overall, the results point to novel pathways of tissue-specific regulation of primary and memory antimicrobial CD8 T cell responses.
使用MHC I类四聚体测量肠道黏膜CD8 T细胞对单核细胞增生李斯特菌感染的反应，并与外周血、二级淋巴组织和肝脏中的反应进行比较。为了评估李斯特菌的疫苗接种潜力并分析C57BL/6小鼠品系中的反应，构建了表达OVA的重组李斯特菌（rLM-ova）。感染后9天反应达到峰值，与脾脏相比，肠道黏膜和肝脏中OVA特异性的CD8 T细胞池比例要大得多。然而，这些差异与每个部位的细菌滴度无关。固有层和肝脏中较高的反应导致这些组织中CD8记忆群体更大。此外，诱导的记忆水平取决于感染剂量，并且与口服攻击后的回忆反应强度呈负相关。组织中的回忆反应在固有层和肝脏中最为强烈，重新激活的抗原特异性T细胞产生γ干扰素。CD40或MHC II类缺陷小鼠的感染在肠道黏膜中诱导出较差的CD8 T细胞反应，但仅部分降低了脾脏和肝脏中的反应。总体而言，结果指向了初级和记忆性抗微生物CD8 T细胞反应的组织特异性调节的新途径。
