Circulating Naïve and CD4+CD25high Regulatory T Cells in Patients With Autoimmune Pancreatitis

Abstract

Autoimmune pancreatitis (AIP) is a new clinical entity of pancreatic disorder. There are several immunologic and histological abnormalities specific for the disease, including increased levels of serum IgG4 and infiltration of lymphocytes and IgG4-positive plasmacytes. The role of IgG4 is unclear. Recently, regulatory T cells (Tregs) have been reported to be involved in the development of various autoimmune diseases as well as B cell shifting to IgG4-producing plasmacytes. To clarify the role of Tregs in the pathophysiology of AIP, we analyzed circulating Tregs in AIP. We recruited 27 patients with AIP for this study. For comparison, we also recruited 23 patients with other pancreatic disease and 32 healthy subjects as controls. We analyzed Tregs as CD4+CD25high and CD4+CD25+CD45RA+ (naïve) from peripheral blood by flow cytometry. In peripheral blood, CD4+CD25high Tregs were significantly increased in AIP patients (3.01% T 1.77%) compared with alcoholic chronic pancreatitis (CP) (1.65% T 0.58%), idiopathic CP (1.53% T0.56%), and healthy control (1.72% T 0.81%, P G 0.05). Naïve Tregs significantly decreased in AIP (0.32% T 0.22%) compared with healthy control (0.83% T 0.65%) and CP group (alcoholic and idiopathic CP; 0.52% T 0.40%, P G 0.05). In untreated AIP patients,the number of CD4+CD25high Tregs and IgG4 are correlated (R =0.53, P G 0.05). Increased numbers of CD4+CD25high Tregs may influence IgG4 production in AIP, whereas decreased numbers of naïve Tregs may be involved in the pathogenesis of AIP.