Inflammatory bowel disease patients have increased frequency of circulating TcdB-specific CD4+ T cells. A, Representative unstimulated and TcdB-stimulated CD25/OX40 assay wells for a Crohn’s disease (CD) patient, showing gating strategy as previously described8 for CD25+OX40+ cells and T helper type 1 (Th1), Th2, and Th17 cells, gates set on CD4+ T cells and CD3neg cells. B, Comparison of TcdB-specific CD4+ T cell responses normalized as a percent of Pediacel vaccine responses for healthy control (HC) subjects (n = 20), CD (n = 20), and ulcerative colitis (UC) patients (n = 20). C, Spearman’s rho correlation between Harvey-Bradshaw index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC; and TcdB-specific CD4+ T cells (n = 20 CD and n = 20 UC). D, Levels of anti-TcdB and anti-TcdBCROPS immunoglobulin G (IgG) and IgA for cohorts in panel B measured by enzyme-linked immunosorbent assay. Statistical analysis in panels B and D used Kruskal-Wallis tests.