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

  • ️Tue Jan 01 2019

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

Britt Roosenboom et al. Inflamm Bowel Dis. 2019.

Abstract

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.

Keywords: CD103; CD69; IBD; translational immunology.

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Figures

FIGURE 1.
FIGURE 1.

Baseline percentages of CD103+, CD103+CD4+, CD103+CD8+, CD103-CD4+, and CD103-CD8+ within CD3+ T lymphocytes and the ratio CD4+/CD8+ T lymphocytes explored with FACS analysis on colonic biopsies of UC and CD patients with active colon disease compared with healthy controls. *Significant P value.

FIGURE 2.
FIGURE 2.

Baseline percentages of CD103+, CD103+CD4+, CD103+CD8+, CD103-CD4+, and CD103-CD8+ within CD3+ T-lymphocytes and the ratio CD4+/CD8+ T-lymphocytes explored with FACS analysis on ileal biopsies of CD patients with active ileal disease compared with healthy controls. *Significant P value.

FIGURE 3.
FIGURE 3.

Representative flow cytometric analyses of CD103+CD4+, CD103+CD8+, CD103-CD4+, and CD103-CD8+ within CD3+ T-lymphocytes on (A) colonic biopsies of a CD patient with moderate to severe colonic disease during baseline and follow-up endoscopy, (B) colonic biopsies of a CD patient with moderate to severe colonic disease during baseline endoscopy and inactive disease during follow-up endoscopy, and (C) colonic biopsies of a healthy control.

FIGURE 4.
FIGURE 4.

Intra-individual fold change, expressing the ratio between follow-up and baseline percentages of the different intestinal lymphocyte subsets with either active or inactive endoscopic disease (A, CD3, CD4, CD8; B, CD103+, CD103+CD4+, CD103+CD8+; C, CD103-CD4+, CD103-CD8+). ● Active UC (n = 13). ○ Inactive UC (n = 7). ▲Active colon CD (n = 9). ∆ Inactive colon CD (n = 10). ■ Active ileum CD (n = 6). □ Inactive ileum CD (n = 17). *Significant P value ≤0.05.

FIGURE 5.
FIGURE 5.

Percentages of the different intestinal lymphocyte subsets at follow-up endoscopy (A, CD3, CD4, CD8; B, CD103+, CD103+CD4+, CD103+CD8+; C, CD103-CD4+, CD103-CD8+). ● Active colon IBD (n = 22). ○ Inactive colon IBD (n = 17). ■ Colon healthy control (n = 16). ▲Active ileum CD (n = 6). ∆ Inactive ileum CD (n = 17). ■ Ileum healthy control (n = 5). *Significant P value ≤0.05.

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