Increased Apoptosis of Regulatory T Lymphocytes in Patients with Active Autoimmune Hepatitis

Autoimmune hepatitis (AIH) is characterized by autoimmune-mediated inflammatory liver injuries which require a life-long immunosuppressive therapy. The pathophysiology of AIH remains largely unknown. There is increasing evidence that impairment of regulatory T cells (Tregs) may cause autoimmune diseases. However, the frequency and function of Tregs (CD4 CD25^highCD127^low/^-FOXP3) in the blood are not reduced in AIH patients compared to healthy subjects. Moreover, patients with active AIH revealed even a higher number of Tregs compared to patients in remission. We therefore investigated whether Tregs from blood of patients with active AIH reveal increased apoptosis and might therefore numerically not be sufficient for disease control despite their increased number. Treg cell apoptosis was assessed by flow-cytometric detection of the percentage of annexin-V-positive cells in the Treg cell population. We demonstrated increased apoptosis of Tregs in patients with active AIH compared to those with remission or healthy individuals. We also observed elevated Teff cell apoptosis in active AIH, but to a lower percentage as compared to Treg cell apoptosis. The increased apoptosis of Tregs in patients with active AIH was accompanied by enhanced caspase activity in the serum. In conclusion, enhanced Treg cell apoptosis and the resulting insufficient increase of Treg cell number might represent one explanation for the lack of disease control and ongoing liver injury in patients with active AIH which is mirrored by increased caspase activity in the serum.