Gastroenterology
Volume 138, Issue 3 , Pages 1178-1188 , March 2010

Chronic Pancreatitis Is Associated With Disease-Specific Regulatory T-Cell Responses

  • Hubertus Schmitz–Winnenthal

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Dong–Ho Kim Pietsch

      Affiliations

    • Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
    • ,
  • Simon Schimmack

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Andreas Bonertz

      Affiliations

    • Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
    • ,
  • Florian Udonta

      Affiliations

    • Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
    • ,
  • Yingzi Ge

      Affiliations

    • Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
    • ,
  • Luis Galindo

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Sebastian Specht

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Christine Volk

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • Department of Hematology, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Kaspar Zgraggen

      Affiliations

    • Berner Viszeralchirurgie and Schweizerisches Pankreaszentrum Klinik Beau-Site Bern, Bern, Switzerland
    • ,
  • Moritz Koch

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Markus W. Büchler

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Jürgen Weitz

      Affiliations

    • Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
    • ,
  • Philipp Beckhove

      Affiliations

    • Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
    • Corresponding Author InformationReprint requests Address requests for reprints to: Philipp Beckhove, MD, Translational Immunology Unit, The German Cancer Research Center, Heidelberg, INF 280, 69120 Heidelberg, Germany

Received 24 November 2008 ,Accepted 9 November 2009.

References 

  1. Friess H, Buchler MW, Mueller C, et al. Immunopathogenesis of chronic pancreatitis. Gastroenterology. 1998;115:1018–1022
  2. Zamboni G, Luttges J, Capelli P, et al. Histopathological features of diagnostic and clinical relevance in autoimmune pancreatitis: a study on 53 resection specimens and 9 biopsy specimens. Virchows Arch. 2004;445:552–563
  3. Lin LF, Huang PT, Ho KS, et al. Autoimmune chronic pancreatitis. J Chin Med Assoc. 2008;71:14–22
  4. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrations in patients with sclerosing pancreatitis. N Engl J Med. 2001;344:732–738
  5. Zen Y, Fujii T, Harada K, et al. Th2 and regulatory immune reactions are increased in immunoglobin G4-related sclerosing pancreatitis and cholangitis. Hepatology. 2007;45:1538–1546
  6. Hunger RE, Mueller C, Z'Graggen K, et al. Cytotoxic cells are activated in cellular infiltrates of alcoholic chronic pancreatitis. Gastroenterology. 1997;112:1656–1663
  7. Saurer L, Reber P, Schaffner T, et al. Differential expression of chemokines in normal pancreas and in chronic pancreatitis. Gastroenterology. 2000;118:356–367
  8. Ockenga J, Jacobs R, Kemper A, et al. Lymphocyte subsets and cellular immunity in patients with chronic pancreatitis. Digestion. 2000;62:14–21
  9. Gansauge F, Gansauge S, Eh M, et al. Distributional and functional alterations of immunocompetent peripheral blood lymphocytes in patients with chronic pancreatitis. Ann Surg. 2001;233:365–370
  10. Grundsten M, Liu GZ, Permert J, et al. Increased central memory T cells in patients with chronic pancreatitis. Pancreatology. 2005;5:177–182
  11. Wekerle H. The viral triggering of autoimmune disease. Nat Med. 1998;4:770–771
  12. Vallance BA, Hewlett BR, Snider DP, et al. T cell-mediated exocrine pancreatic damage in major histocompatibility complex class II-deficient mice. Gastroenterology. 1998;115:978–987
  13. Gonnet-Gracia C, Barnetche T, Richez C, et al. Anti-nuclear antibodies, anti-DNA and C4 complement evolution in rheumatoid arthritis and ankylosing spondylitis treated with TNF-α blockers. Clin Exp Rheumatol. 2008;26:401–407
  14. Okazaki K, Uchida K, Ohana M, et al. Autoimmune-related pancreatitis is associated with autoantibodies and a Th1/Th2-type cellular immune response. Gastroenterology. 2000;118:573–581
  15. Feuerer M, Beckhove P, Bai L, et al. Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nat Med. 2001;7:452–458
  16. Muller-Berghaus J, Ehlert K, Ugurel S, et al. Melanoma-reactive T cells in the bone marrow of melanoma patients: association with disease stage and disease duration. Cancer Res. 2006;66:5997–6001
  17. Lalvani A, Brookes R, Hambleton S, et al. Rapid effector function in CD8+ memory T cells. J Exp Med. 1997;186:859–865
  18. Hiltbold EM, Ciborowski P, Finn OJ. Naturally processed class II epitope from the tumor antigen MUC1 primes human CD4+ T cells. Cancer Res. 1998;58:5066–5070
  19. Taylor A, Akdis M, Joss A, et al. IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain-containing protein tyrosine phosphatase 1. J Allergy Clin Immunol. 2007;120:76–83
  20. Hawrylowicz CM, O'Garra A. Potential role of interleukin-10-secreting regulatory T cells in allergy and asthma (rev). Nat Rev Immunol. 2005;4:271–283
  21. Tarbell KV, Yamazaki S, Olson K, et al. CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med. 2004;199:1467–1477
  22. Bedossa P, Bacci J, Lemaigre G, et al. Lymphocyte subsets and HLA-DR expression in normal pancreas and chronic pancreatitis. Pancreas. 1990;5:415–420
  23. Schmitz-Winnenthal FH, Escobedo LV, Beckhove P, et al. Specific immune recognition of pancreatic carcinoma by patient-derived CD4 and CD8 T cells and its improvement by interferon-γ. Int J Oncol. 2006;28:1419–1428
  24. Schmitz-Winnenthal FH, Volk C, Z'Graggen K, et al. High frequencies of functional tumor-reactive T cells in bone marrow and blood of pancreatic cancer patients. Cancer Res. 2005;65:10079–10087
  25. Sakaguchi S, Ono M, Setoguchi R, et al. Foxp3+ CD25+ CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol Rev. 2006;212:8–27

 Conflicts of interest The authors disclose no conflicts.

PII: S0016-5085(09)02001-0

doi: 10.1053/j.gastro.2009.11.011

Gastroenterology
Volume 138, Issue 3 , Pages 1178-1188 , March 2010

Article Tools

* Image Usage & Resolution