Frequencies of circulating regulatory TIGIT+CD38+ effector T cells correlate with the course of inflammatory bowel disease

Disease heterogeneity hampers achieving long-term disease remission in inflammatory bowel disease (IBD). Monitoring ongoing tissue-localized regulatory and inflammatory T-cell responses in peripheral blood would empower disease classification. We determined whether regulatory and inflammatory phenotypes of circulating CD38(+) effector (CD62L(neg)CD4(+)) T cells, a population enriched for cells with mucosal antigen specificity, classify disease course in pediatric IBD patients. In healthy individuals, circulating CD38(+) effector T cells had a predominant regulatory component with lower frequencies of IFN gamma-secreting T cells, higher frequencies of IL-10-secreting T cells and higher frequencies of inhibitory molecule T-cell immunoglobulin and ITIM domain(+) (TIGIT) cells than CD38(neg) effector T cells. TIGIT expression was stable upon stimulation and marked CD38(+) T cells with inhibitory properties. In IBD patients with active intestinal inflammation this predominant regulatory component was lost: circulating CD38(+) effector T cells had increased activated CD25(+) CD45RA(neg) and decreased TIGIT(+) cell frequencies. TIGIT percentages below 25% before treatment associated with shorter duration of clinical remission. In conclusion, phenotypic changes in circulating CD38(+) effector T cells, in particular the frequency of TIGIT(+) cells, classify pediatric IBD patients and predict severity of disease course. These findings have relevance for IBD and can be exploited in graft-versus-host-disease and checkpoint inhibitor-induced inflammation in cancer.