Pro-inflammatory innate-like T cells are expanded in the blood and inflamed intestine in Crohn’s Disease

ABSTRACT A complex and tissue-specific network of cells including T lymphocytes maintains intestinal homeostasis. To address disease and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with Crohn’s disease (CD) and healthy donor PBMCs. We compared inflamed and not inflamed tissue areas of bowel resections. Chronic inflammation enforced activation, exhaustion and terminal differentiation of CD4 + and CD8 + T cells and an enrichment of CD4 + Foxp3 + cells (Tregs) in inflamed intestine. However, tissue-repairing Tregs decreased, while enigmatic rare Foxp3 + T-cell subsets appeared upon inflammation. In vitro assays revealed that those subsets, e.g. CD4 + Foxp3 + HLA-DR + TIGIT − and CD4 + Foxp3 + CD56 + , express pro-inflammatory IFN-γ. Some T-conventional (Tcon) cells tended towards innateness. In blood of CD patients, not well studied CD4 + and CD8 + subsets of CD16 + CCR6 + CD127 + T cells appeared anew, a phenotype reproducible by incubation of healthy blood T cells with patient blood plasma. Together, these findings suggest a bias towards innate-like pro-inflammatory Tregs and innate-like Tcon, which act with less specific cytotoxicity. Most likely, this is both cause and consequence of intestinal inflammation during CD. Graphical Abstract