Chronic Pancreatitis Is Associated With Disease-Specific Regulatory T-Cell Responses
Received 24 November 2008; accepted 9 November 2009. published online 19 November 2009. Uncorrected Proof
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)-γ, 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-γ secretion. Pancreatitis-specific IL-10 responses were mediated by IL-10+IFN-γ−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-γ, suggesting pancreatitis-specific activity of regulatory T cells in situ.
Conclusions
Chronic pancreatitis is associated with disease-specific regulatory T-cell responses.
⁎Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
‡Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
§Department of Hematology, University Hospital of Heidelberg, Heidelberg, Germany
∥Berner Viszeralchirurgie and Schweizerisches Pankreaszentrum Klinik Beau-Site Bern, Bern, Switzerland
Reprint requests Address requests for reprints to: Philipp Beckhove, MD, Translational Immunology Unit, The German Cancer Research Center, Heidelberg, INF 280, 69120 Heidelberg, Germany
Conflicts of interest The authors disclose no conflicts.
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