Circulating CD4+CD25+ Regulatory T Cells in the Pathobiology of Ulcerative Colitis and Concurrent Primary Sclerosing Cholangitis

BACKGROUND: Immunopathogenetic features of primary sclerosing cholangitis (PSC) in ulcerative colitis (UC) still remains unclear. Peripheral blood CD4+CD25+ regulatory T cells have a key role in the induction and maintenance of peripheral self-tolerance and inhibit several organ-specific autoimmune diseases. Therefore, CD4+CD25+ T cells are believed to play an essential role in autoimmune diseases. The aim of the present study is to analyze the role of CD4+CD25+ T cells in the pathogenesis of UC-associated PSC. METHODS: This study evaluated the levels of CD4+CD25+ T cells in peripheral blood mononuclear cells (PBMC) of 27 UC patients with PSC and 20 UC patients as controls. CD4+CD25+ T cells were isolated from PBMC with a direct immunofluorescence technique, using mice monoclonal antibodies namely FITC-labeled anti-CD4 and PE-labeled anti-CD25. In each patient, CD4+CD25+ T cells percentage in PBMC were studied by flow cytometry, and then the number of CD4+CD25+ T cells were calculated. RESULTS: Twenty-seven UC patients with PSC and 20 UC patients without PSC as controls were enrolled in the present study. The percentage of CD4+CD25+ regulatory T cells among PBMC were significantly elevated in UC + PSC patients compared with UC patients without PSC (p = 0.04). CONCLUSIONS: CD4+CD25+ T cells were found to be elevated in UC patients with PSC suggesting a partial role of activated T cell response in the disease pathophysiology. Our findings imply that CD4+CD25+ regulatory T cells may play a key role in the immunopathogenesis of UC-associated PSC and may affect the therapeutic management of these diseases.