Experimental immune-mediated pancreatitis in neonatally thymectomized mice immunized with carbonic anhydrase II and lactoferrin.
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.
Uchida
Kazushige
K
Department of Gastroenterology and Endoscopic Medicine, Kyoto University Hospital, Kyoto, Japan.
Okazaki
Kazuichi
K
Nishi
Toshiki
T
Uose
Suguru
S
Nakase
Hiroshi
H
Ohana
Masaya
M
Matsushima
Yumi
Y
Omori
Katsuyuki
K
Chiba
Tsutomu
T
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D024402:Carbonic Anhydrase II / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007114:Immunization; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D007781:Lactoferrin / Q000008:administration & dosage* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010179:Pancreas / Q000276:immunology; D010195:Pancreatitis / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D013934:Thymectomy
D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D007781:Lactoferrin; D024402:Carbonic Anhydrase II