A high proportion of activated memory CD8+ T cells and paucity of Treg characterise the gastrointestinal tissue of patients with IN-COL.
We first sought to understand the pathogenesis of IN-COL by direct study of affected tissue. Patients with IN-COL had a T cell lymphocytosis (13% of lymphocytes) compared with those in the IN-NAE group (3%; p<0.01; Figure 2ai). This could not be explained simply by a rise in total CD4+ or CD8+ T cells (Figure 2aiii and v). IN-treated patients had an inverted CD4:CD8 ratio in the gut tissue (i.e. a predominance of CD8+ T cells), which was distinct from both healthy volunteer gut and tissue from patients with UC (Figure 2aiii and v). However, perturbations in the CD4:CD8 ratio did not differentiate between the IN-COL and IN-NAE groups. The proportion of activated memory CD4+ T cells was significantly elevated in GMNC of patients with IN-COL (22% of CD4+ T cells) compared with the IN-NAE group (1%; p<0.01; Figure 2aiv). The proportion of activated memory CD8+ T cells was significantly elevated in GMNC of patients with IN-COL (52% of CD8+ T cells) compared with the IN-NAE group (3%; p<0.01; Figure 2avi) and also with the UC group (10%; p<0.01; Figure 2avii). The proportion of activated memory CD8+ T cells was numerically greater than the proportion of activated memory CD4+ T cells. The proportion of activated memory CD8+ T cells was elevated in the GMNC of patients with UC (10% of CD8+T cells) compared with healthy volunteers (1%; p<0.01; Figure 2avi). Patients with UC had elevated proportion of Treg (CD4+25+FOXP3+) compared with healthy volunteers (6% of CD4+ T cells compared with 1% p<0.01; Figure 2aii and 2b) and with IN-COL patients (3% p<0.01; Figure 2aii and 2b). Patients with IN-COL did not have elevated proportion of Treg compared with IN-NAE (3% compared to 1%; Figure 2aii).