A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice
Carl-Philipp Hackstein, Dana Costigan, Linnea Drexhage, Claire Pearson, Samuel J. Bullers, Nicholas E. Ilott, Hossain Delowar Akther, Yisu Gu, Michael Fitzpatrick, Oliver J. Harrison, Lucy C. Garner, Elizabeth H. Mann, Sumeet Pandey, Matthias Friedrich, Nicholas M. Provine, Holm H. Uhlig, Emanuele Marchi, Fiona Powrie, Paul Klenerman, Emily Thornton
Abstract
Interactions with commensal microbes shape host immunity on multiple levels and play a pivotal role in human health and disease. Tissue-dwelling, antigen-specific T cells are poised to respond to local insults, making their phenotype important in the relationship between host and microbes. Here we show that MHC-II restricted, commensal-reactive T cells in the colon of both humans and mice acquire transcriptional and functional characteristics associated with innate-like T cells. This cell population is abundant and conserved in the human and murine colon and endowed with polyfunctional effector properties spanning classic Th1- and Th17-cytokines, cytotoxic molecules, and regulators of epithelial homeostasis. T cells with this phenotype are increased in ulcerative colitis patients, and their presence aggravates pathology in dextran sodium sulphate-treated mice, pointing towards a pathogenic role in colitis. Our findings add to the expanding spectrum of innate-like immune cells positioned at the frontline of intestinal immune surveillance, capable of acting as sentinels of microbes and the local cytokine milieu.