Final Report
Proposal No. IBD-0143
Principal Investigator: Rainer Duchmann, M.D.
Applicant Organization: Charité - Universitätsmedizin Berlin; Campus Benjamin Franklin (Germany)
Project Title: CD4+CD25+ T regulatory cells in inflammatory bowel disease
Period of Award: May 15, 2005 – August 14, 2007
Regulatory CD25+ T cells can prevent and even cure established inflammatory bowel disease in mice. However, their role in human IBD is still in a very early stage of exploration.
We analyzed, if CD4+CD25+ Treg differ between healthy donors and IBD patients regarding their quantity, phenotype or function.
We quantified peripheral Treg with the established intracellular marker FOXP3 in combination with CD25 in IBD patients during the course of disease. We enrolled a heterogeneous group of patients, partially with complicated courses of disease. We could not demonstrate a general correlation of peripheral Treg levels with disease activity. With our phenotypic analysis we identified Treg with the potential to migrate to the skin, gut and also to mucosal lymph nodes. Unfortunately, the frequency of the identified subsets did not differ between healthy donors and IBD patients. The only difference identified so far is a lower level of the chemokine receptor CCR4 on Treg of CD patient compared to healthy controls. With our functional experiments we could show, that isolated CD4+CD25+ Treg can suppress the secretion of pro-inflammatory cytokines of effector T cells after stimulation with bacterial proteins.
In our hands, the number of peripheral Treg cannot be used as immunological marker to monitor the course of disease, e.g. to predict a relapse or response to medical treatment in IBD. We enrolled a more heterogeneous group of patients than initially indented. However, this group represents the typical patients in our clinic and is possibly representative for IBD patients under real circumstances. The decreased expression of the chemokine receptor CCR4 on Treg of IBD patients may provide a pathomechanism in IBD, leading to a defective homing of Treg into the gut.