Naive T Cells in the Gut of Newly Diagnosed, Untreated Adult Patients with Inflammatory Bowel Disease

Background: The phenotype of the T-cell subpopulations and their related cytokine networks in the gastrointestinal mucosa of patients with inflammatory bowel disease can potentially be used as a predictive value for clinical course and response to therapy. Here, we analyzed T-cell subpopulations in newly diagnosed, untreated adult patients and correlated them with clinical presentation.

Methods: Mucosal biopsies from duodenum, ileum, and colon mucosa of patients with Crohn's disease and ulcerative colitis and controls were obtained. The simple endoscopy score in Crohn's disease and the full Mayo score in ulcerative colitis were used to score disease activity. Mucosa-infiltrating T cells were characterized by flow cytometric immunophenotyping and were stimulated to assess cytokine secretion.

Results: Based on the expression of the maturation and activation markers CD45RA and CD27, we identified 4 different profiles. Profile A contained mainly CD45RA(+)CD27(+) naive T cells; profile B contained mainly CD45RA(-)CD27(+) central memory T cells; profile C contained mainly CD45RA(-)CD27(-) effector memory T cells; and profile D consisted of similar percentages of these aforementioned subpopulations. Profile A was only observed in the ileum/colon of patients with inflammatory bowel disease, associated with upper gastrointestinal location and perianal disease in Crohn's disease and expressed more tumor necrosis factor alpha and less interferon gamma. In contrast, profile D was restricted to controls. There was no correlation between the different T-cell profiles and endoscopic disease activity.

Conclusions: Newly diagnosed patients with inflammatory bowel disease display different T-cell maturation profiles in the gut mucosa, corresponding to distinct cytokine responses. Follow-up studies are needed to determine whether the profiles associate with clinical course and response to therapy.