Intestinal CD103(+)CD4(+) and CD103(+)CD8(+) T-Cell Subsets in the Gut of Inflammatory Bowel Disease Patients at Diagnosis and During Follow-up

BACKGROUND: The integrin CD103 is proposed to be a potential therapeutical target in inflammatory bowel disease (IBD), as it can form a heterodimeric integrin with β7 (Etrolizumab, anti-β7 integrin) on epithelial T cells. Therefore, we aimed to study the frequencies of different intestinal CD103(+)T-cell subsets, both CD4(+) and CD8(+), in newly diagnosed, untreated IBD patients at baseline and during follow-up, compared with healthy controls. METHODS: Intestinal biopsies from inflamed segments during colonoscopy and peripheral blood samples were prospectively taken from IBD patients at diagnosis and during follow-up. Blood and single cell suspensions from biopsies were analyzed for CD103(+) T-cell subpopulations by flow cytometry and expressed as median percentages of the total T-cell population. RESULTS: In total, 75 Crohn’s disease (CD) patients, 49 ulcerative colitis (UC) patients, and 16 healthy controls were included. At presentation, IBD patients displayed lower percentages of CD103(+)T-cell subsets in inflamed biopsies: 3% (1 to 5) CD103(+)CD4(+) in IBD vs 5% (5 to 7) in healthy controls (P = 0.007) and 9% (4 to 15) CD103(+)CD8(+) compared with 42% (23 to 57) in healthy controls (P = 0.001). The majority of intestinal T cells was composed of CD103(-)CD4(+) T cells (65% [52 to 74]) in IBD compared with 30% (21 to 50) in healthy controls (P = 0.001). In patients with endoscopic remission during follow-up (n = 27), frequencies of CD103(+) and CD103(-)T-cell subsets were comparable with healthy controls. CONCLUSION: At diagnosis, active inflammation in IBD was associated with decreased percentages of both CD103(+)CD4(+) and CD103(+)CD8(+)T-cell subsets in colon and ileum biopsies. In active disease during follow-up, these T-cell populations remained low but increased in remission to values comparable with healthy controls. A shift toward more CD103(-)T cells was observed during active inflammation.