Circulating and Tissue-Resident CD4+ T Cells With Reactivity to Intestinal Microbiota Are Abundant in Healthy Individuals and Function Is Altered During Inflammation

作者：Ahmed N. Hegazy, Nathaniel R. West, Michael J. T. Stubbington, Emily Wendt, Kim Suijker, Angeliki Datsi, Sébastien This, Camille Danne, Suzanne Campion, Sylvia H. Duncan, Benjamin M. J. Owens, Holm H. Uhlig, Andrew J. McMichael, Andreas Bergthaler, Sarah A. Teichmann, Satish Keshav, Fiona Powrie · 发表于：Gastroenterology · 年份：2017 · DOI：10.1053/j.gastro.2017.07.047 · 被引用次数：345 · 研究领域：Gut microbiota and health、T-cell and B-cell Immunology、IL-33, ST2, and ILC Pathways

Background & Aims Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4 + T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation. Methods We collected samples of peripheral blood mononuclear cells and intestinal tissues from healthy individuals (controls, n = 13−30) and patients with inflammatory bowel diseases (n = 119; 59 with ulcerative colitis and 60 with Crohn's disease). We used 2 independent assays (CD154 detection and carboxy-fluorescein succinimidyl ester dilution assays) and 9 intestinal bacterial species ( Escherichia coli, Lactobacillus acidophilus, Bifidobacterium animalis subsp lactis, Faecalibacterium prausnitzii, Bacteroides vulgatus, Roseburia intestinalis, Ruminococcus obeum, Salmonella typhimurium, and Clostridium difficile ) to quantify, expand, and characterize microbe-reactive CD4 + T cells. We sequenced T-cell receptor Vβ genes in expanded microbe-reactive T-cell lines to determine their clonal diversity. We examined the effects of microbe-reactive CD4 + T cells on int...