Circulating naive and CD4+CD25high regulatory T cells in patients with autoimmune pancreatitis

Objective: 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. Methods: 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(+)CD25(high) and CD4(+)CD25(+)CD45RA(+) (naive) from peripheral blood by flow cytometry. Results: In peripheral blood, CD4(+)CD25(high) Tregs were significantly increased in AIP patients (3.01% +/- 1.77%) compared with alcoholic chronic pancreatitis (CP) (1.65% +/- 0.58%), idiopathic CP (1.53% +/- 0.56%), and healthy control (1.72% +/- 0.81%, P < 0.05). Naive Tregs significantly decreased in AIP (0.32% +/- 0.22%) compared with healthy control (0.83% +/- 0.65%) and CP group (alcoholic and idiopathic CP; 0.52% +/- 0.40%, P G 0.05). In untreated AIP patients, the number of CD4(+)CD25(high) Tregs and IgG4 are correlated (R = 0.53, P < 0.05). Conclusions: Increased numbers of CD4(+)CD25(high) Tregs may influence IgG4 production in AIP, whereas decreased numbers of naive Tregs may be involved in the pathogenesis of AIP.