4th Annual BMRP Investigator Meeting - Abstract

CD4+CD25+ T Regulatory Cells in Inflammatory Bowel Disease

Kerstin Büchner^b, Jochen Maul and Rainer Duchmann^a

Medizinische Klinik I, Charitè-Universitätsmedizin Berlin, Campus Benjamin Franklin (Berlin, Germany)

Intestinal immune responses are regulated by both specialized inflammatory and regulatory T cell (Treg) populations. Based on previous results from our group, we now determine whether differences in the frequency of Treg or Treg subsets in peripheral blood of IBD patients can serve as a subclinical marker of disease activity and investigate basic mechanisms of the activation and suppressive function of Treg in inflammatory bowel disease (IBD).

In our clinical cohort, preliminary time course analysis identified individual patients with decreased frequency of Treg in active disease and increased frequency of Treg in remission. However, this does not seem to be a consistent finding and overall correlation between Treg frequency and disease activity was less clear than in previous studies. With regard to Treg subtypes, we found that expression of CCR4, CD62L or CTLA-4 on CD4+CD25high T cells was not different between IBD and healthy controls. Using a combined staining for FOXP3 and CD25 we could identify subsets with different homing potential within the CD25+FOXP3+ Treg. Treg expressing the skin homing marker CLA were more frequent compared to gut homing Treg that express integrin 7. This, however, was independent of IBD activity.

We previously have shown that regulatory T cells from IBD patients retain their suppressive activity using polyclonal stimuli. To dissect a potentially insufficient stimulation of regulatory T cells in IBD patients after activation with bacterial antigens, we are establishing assays for an antigen-specific suppression using freshly isolated and in vitroexpanded regulatory T cells.

^aPrincipal Investigator; ^bCo-Investigator and Presenter