Autoimmune pancreatitis (AIP) is a newly recognized pancreatic disorder. Recently, International Consensus Diagnostic Criteria for AIP (ICDC) was published. In this ICDC, AIP was classified into Type 1 and Type 2. Patients with Type 1 AIP have several immunologic and histologic abnormalities specific to the disease, including increased levels of serum IgG4 and storiform fibrosis with infiltration of lymphocytes and IgG4-positive plasmacytes in the involved organs. Among the involved organs showing extrapancreatic lesions, the bile duct is the most common, exhibiting sclerosing cholangitis (IgG4-SC). However, the role of IgG4 is unclear. Recently, it has been reported that regulatory T cells (Tregs) are involved in both the development of various autoimmune diseases and the shift of B cells toward IgG4, producing plasmacytes. Our study showed that Tregs were increased in the pancreas with Type 1 AIP and IgG4-SC compared with control. In the patients with Type 1 AIP and IgG4-SC, the numbers of infiltrated Tregs were significantly positively correlated with IgG4-positive plasma cells. In Type 1 AIP, inducible costimulatory molecule (ICOS)+ and IL-10+ Tregs significantly increased compared with control groups. Our data suggest that increased quantities of ICOS+ Tregs may influence IgG4 production via IL-10 in Type 1 AIP. 1. Introduction In 1961, Sarles et al. observed the first case of idiopathic chronic pancreatitis with hypergammaglobulinemia, in which an autoimmune mechanism was supposedly involved [1]. In 1991, Kawaguchi et al. reported two cases of an unusual lymphoplasmacytic sclerosing inflammatory disease involving the entire pancreas, common bile duct, gallbladder, and, in one patient, the lip [2]. In addition, two patients presented mass-like enlargement of the pancreatic head. Histopathological characteristics included diffuse lymphoplasmacytic infiltration, marked interstitial fibrosis, acinar atrophy, and obliterative phlebitis of the pancreatic and portal veins, which was termed as lymphoplasmacytic sclerosing pancreatitis (LPSP). In 1995, Yoshida et al. first proposed the concept of “autoimmune pancreatitis (AIP),” in which patients showed a diffusely enlarged pancreas, a narrowing pancreatogram, increased serum IgG, the presence of autoantibodies, fibrotic changes with lymphocytic infiltration, and steroidal efficacy [3]. In 2001, Hamano et al. reported that elevated serum IgG4 levels were highly specific and sensitive for the diagnosis of AIP [4]. In 2003, Kamisawa et al. suggested that AIP is a systemic disease, based on the findings that
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