CD4+CD25+ but not CD4+Foxp3+ T cells as a regulatory subset in primary biliary cirrhosis

Increasing evidence indicates a role for regulatory T cells (Tregs) in the immune response and in autoimmune diseases, but the role of Tregs and cytokines in autoimmune hepatic diseases remains largely unclear and controversial, especially in patients with primary biliary cirrhosis (PBC). This study was undertaken to investigate Tregs and different cytokines in the liver and peripheral blood of PBC patients. We found that these patients demonstrated a reduction of CD4(+)CD25(+) T cells but elevated CD4(+)Foxp3(+) T cells in peripheral blood mononuclear cells (PBMCs) and CD4(+) T cells. The percentage of CD4(+)CD25(+) T cells in PBMCs was negatively correlated with elevated plasma interferon (IFN)-gamma levels. A liver-specific analysis showed that the frequency of Foxp3(+) Tregs, transforming growth factor (TGF)-beta 1 and IFN-gamma were increased in PBC patients. Our findings suggest that an imbalance between CD4(+)CD25(+) Tregs and cytotoxic cytokines plays a crucial role in the pathogenesis of PBC while the role of Foxp3 needs further investigation. Cellular & Molecular Immunology (2010) 7, 485-490; doi: 10.1038/cmi.2010.40; published online 23 August 2010