Regulatory CD25+ T cells (T_reg) are effective in the prevention and down-regulation of inflammatory bowel disease (IBD) in animal models. Functional T_reg cells are characterized by the expression of the transcription factor FOXP3 and show a CD4+CD25^high phenotype in humans. The aim of this study was to determine whether disease activity in IBD correlates with changes in frequency of T_reg cells and their distribution in the intestinal mucosa.

T_reg cells were analyzed from peripheral blood and from biopsy specimens of IBD patients, inflammatory controls, and healthy volunteers by flow cytometry (CD4+CD25^high), immunochemistry (FOXP3), and real-time PCR (FOXP3). Regulatory properties of purified peripheral CD4+CD25^high T_reg cells were determined by their suppressive effect on the proliferation of CD4+CD25− T cells.

In peripheral blood, CD4+CD25^high T cells from IBD patients retain their suppressive activity. CD4+CD25^high and FOXP3+ T_reg cells are increased during remission but decreased during active disease. This contrasts with their strong increase in peripheral blood of patients with acute diverticulitis. Different than peripheral blood, inflamed IBD mucosa contains an increased number of CD4+CD25^high T cells, FOXP3+ T cells, and transcripts for FOXP3 compared with noninflamed mucosa. However, the increase of FOXP3+ T cells in IBD lesions is significantly lower compared with inflammatory controls.

The frequency of CD4+CD25+ T_reg cells varies with IBD activity. Active IBD is not associated with a functional defect but with a contraction of the peripheral blood T_reg pool and an only moderate expansion in intestinal lesions. Thus, compensatory mechanisms, numerically, are not successfully achieved in these diseases.