Fates of Commensal Specific, Innate-like CD8 +T cells in the Gut

Abstract

Abstract Barrier tissues such as the skin and gut are host to a variety of microbes collectively termed the microbiota. To maintain host homeostasis, sufficient exposure to the microbiota is necessary, however, diseases such as Inflammatory Bowel Disease (IBD), have been described as occurring amidst breakdown in the normal communication between host and microbe. Fundamentally, IBD is a disease of aberrant immune activation to the microbiota and epithelial barrier dysfunction. At the skin barrier, we have previously described the H2-M3 restricted, CD8 +T cell response in mice after topical exposure to a commensal microbe that aids in barrier maintenance and epithelial repair. However, the residence of these H2-M3 restricted, commensal specific T cells in the gut, and potential contribution to barrier function in this tissue is unknown. We have now identified H2-M3 restricted CD8 +T cells populating the lamina propria and intraepithelial compartments of both the colon and small intestine following novel commensal exposure. Further, during inflammatory conditions these cells drastically expand and produce pro-inflammatory Type 1 cytokines. Following these discoveries, we have developed novel tetramer reagents to track and interrogate the function of H2-M3 restricted T cell responses to Helicobacter hepaticus, a common gut commensal with known roles in perpetuating colitis in immunocompromised animals. Utilizing these tools, we hope to uncover how these non-classically restricted immune responses to the same commensal under homeostatic or inflammatory conditions differ, to identify potential targets to correct aberrant reactivity to the microbiota during colitis. NIH-Oxford Cambridge Scholars Program