CD4(+) memory T cell (T(M)) reactivation drives chronicity in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis. Defects driving loss of T(M) regulation likely differ between patients but remain undefined. In health, approximately 40 % of circulating gut-homing CD38(+)T(M) express co-inhibitory receptor T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). TIGIT(+)CD38(+)T(M) have regulatory function while TIGIT(neg)CD38(+)T(M) are enriched in IFN-gamma-producing cells. We hypothesized TIGIT(neg)CD38(+)T(M) are inflammatory and drive disease in a subgroup of IBD patients. We characterized TIGIT(+)CD38(+)T(M) in a uniquely large cohort of pediatric IBD patients from time of diagnosis into adulthood. Circulating TIGIT(neg)CD38(+)T(M) frequencies were higher in a subgroup of therapy-naive CD patients with high plasma IFN-gamma and a more severe disease course. TIGIT(neg)CD38(+)T(M) were highly enriched in HLA-DR(+) and ex-Th17/Th1-like cells, high producers of IFN-gamma. Cultures of healthy-adult-stimulated T(M) identified IL-12 as the only IBD-related inflammatory cytokine to drive the pathogenic ex-Th17-TIGIT(neg)CD38(+) phenotype. Moreover, IL12RB2 mRNA expression was higher in TIGIT(neg)CD38(+)T(M) than TIGIT(+)CD38(+)T(M), elevated in CD biopsies compared to controls, and correlated with severity of intestinal inflammation. Overall, we argue that in a subgroup of pediatric CD, increased IL-12 signaling drives reprogramming of Th17 to inflammatory Th1-like TIGIT(neg)CD38(+)T(M) and causes more severe disease.