Chronic pancreatitis is associated with disease-specific regulatory T-cell responses

Gastroenterology. 2010 Mar;138(3):1178-88. doi: 10.1053/j.gastro.2009.11.011. Epub 2009 Nov 18.


Background & aims: Chronic pancreatitis is characterized by alternating phases of acute inflammation and quiescent disease. Involvement of T-cell responses has been suggested, but pancreatitis-specific T cells have not been described.

Methods: We characterized T-cell responses against pancreatitis, pancreatic carcinoma-associated antigens, and tetanus toxoid in the bone marrow, blood, and/or pancreatitis lesions of patients with pancreatitis, pancreatic cancer, and healthy individuals. T cells were functionally characterized by antigen-dependent secretion of interferon (IFN)-gamma, interleukin (Il)-4, and IL-10, which indicate type 1, type 2, or regulatory T-cell responses, respectively. Regulatory T cells were characterized by multicolor flow cytometry. Isolated regulatory T cells were tested for their capacity to recognize pancreatitis-associated antigens and to suppress conventional T cells in an antigen-dependent manner. T cell-derived cytokines in tissue lesions were quantified by enzyme-linked immunosorbent assay.

Results: Chronic pancreatitis patients showed similar to pancreatic cancer patients and healthy individuals type 1 T-cell responses against tetanus toxoid; however, they exhibited strong IL-10-based T-cell responses against pancreatitis-associated but not pancreatic carcinoma-associated antigens. T cells from pancreatic cancer patients responded to pancreatic cancer-associated but not pancreatitis-associated antigens with IFN-gamma secretion. Pancreatitis-specific IL-10 responses were mediated by IL-10(+)IFN-gamma(-)FoxP3(+) regulatory T cells, which were expanded in the blood, bone marrow, and pancreatitis lesions and possessed the potential to suppress the proliferation of autologous conventional T cells in an antigen-specific manner. Pancreatitis lesions, in comparison with pancreatic carcinomas, contained increased concentrations of IL-10 and reduced levels of IFN-gamma, suggesting pancreatitis-specific activity of regulatory T cells in situ.

Conclusions: Chronic pancreatitis is associated with disease-specific regulatory T-cell responses.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, Neoplasm / immunology
  • Bone Marrow Cells / immunology*
  • Carcinoma / immunology*
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Immunologic Memory*
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-4 / metabolism
  • Pancreas / immunology*
  • Pancreatic Neoplasms / immunology*
  • Pancreatitis, Chronic / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Tetanus Toxoid / immunology


  • Antigens, Neoplasm
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL4 protein, human
  • Tetanus Toxoid
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma