Article

Lab Invest 2002, 82:411–424

Experimental Immune-Mediated Pancreatitis in Neonatally Thymectomized Mice Immunized with Carbonic Anhydrase II and Lactoferrin

Kazushige Uchida1, Kazuichi Okazaki1, Toshiki Nishi1, Suguru Uose1, Hiroshi Nakase1, Masaya Ohana1, Yumi Matsushima1, Katsuyuki Omori2 and Tsutomu Chiba1

  1. 1Department of Gastroenterology and Endoscopic Medicine, Kyoto University Hospital, Kyoto, Japan
  2. 2Central Laboratory, Kyoto University Hospital, Kyoto, Japan

Correspondence: Dr. Kazuichi Okazaki, Department of Gastroenterology and Endoscopic Medicine, Kyoto University Hospital, Shogoin-Kawaracho, Sakyo-ku, Kyoto City, Kyoto, 606-8305, Japan. E-mail: okak@kuhp.kyoto-u.ac.jp

Received 18 October 2001.

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Abstract

We previously reported that autoantibodies against carbonic anhydrase II and lactoferrin are frequently identified in patients with autoimmune-related pancreatitis. To clarify the role of carbonic anhydrase II and lactoferrin, we created animal models of autoimmune pancreatitis by immunizing neonatally thymectomized mice with carbonic anhydrase II and lactoferrin and also by transferring immunized spleen cells to nude mice. Neonatally thymectomized BALB/c mice were immunized with carbonic anhydrase II or lactoferrin followed by three booster injections (n = 10 in each group). We transferred whole, CD4+, or CD8+ spleen cells prepared from immunized neonatally thymectomized mice to nude mice (n = 5 in each group). Gene expression of IFN-gamma and IL-4 was investigated using semiquantitative reverse transcription-polymerase chain reaction. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling staining was used to examine apoptosis. In immunized neonatally thymectomized mice, the prevalence of inflammation was significantly higher in the pancreas. Inflammation was present in all mice receiving whole or CD4+ cells. There was no change in any of the mice receiving CD8+ cells or nonimmunized spleen cells. Carbonic anhydrase II or lactoferrin-immunized mice had apoptotic duct cells or acinar cells, respectively. Expression of the IFN-gamma gene was up-regulated in each group. Similar findings were observed in the salivary glands and liver. An immunologic mechanism against carbonic anhydrase II or lactoferrin is involved in the pathogenesis of these pancreatitis models, in which the effector cells are Th1-type CD4+ T cells.