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

Pancreas. 2008 Mar;36(2):133-40. doi: 10.1097/MPA.0b013e3181577553.


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+CD25high and CD4+CD25+CD45RA+ (naïve) from peripheral blood by flow cytometry.

Results: 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).

Conclusions: 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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / immunology*
  • CD4 Antigens / analysis*
  • Dendritic Cells / immunology
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / blood
  • Humans
  • Immunoglobulin G / blood
  • Immunophenotyping / methods
  • Interleukin-10 / blood
  • Interleukin-2 Receptor alpha Subunit / analysis*
  • Japan
  • Leukocyte Common Antigens / analysis
  • Male
  • Middle Aged
  • Pancreatitis / blood
  • Pancreatitis / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / blood


  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL10 protein, human
  • Immunoglobulin G
  • Interleukin-2 Receptor alpha Subunit
  • Transforming Growth Factor beta
  • Interleukin-10
  • Leukocyte Common Antigens