An experimental model of autoimmune pancreatitis in the rat.
Autoimmune pancreatitis (AIP), a recently defined disease of unknown etiology, is characterized by inflammatory infiltrates in the pancreas with conspicuous involvement of the ducts. The disease clinically manifests in humans as epigastric pain, weight loss, and jaundice. This report describes the development of a novel animal model of this disease in the rat, which we have termed experimental autoimmune pancreatitis. Adoptive transfer of amylase-specific CD4(+) T cells was able to confer pancreatitis to naive syngeneic recipient animals. No treatments before the adoptive transfer of T cells were necessary for disease to ensue, and the severity of disease was proportional to the number of T cells administered. The pancreatic lesions of rats with experimental autoimmune pancreatitis were characterized histologically as overwhelmingly lymphocytic with occasional plasma cells, neutrophils, and mast cells. Acinar tissue destruction and ductular inflammation were common features, with less frequent involvement of larger ducts. Immunohistochemical analysis revealed the presence of CD4(+) T cells in large numbers as well as CD8(+) T cells, macrophages, and dendritic cells. Expression of MHC I and MHC II also increased at the site of the lesion. Clinically, the disease manifested as either failure to gain weight at a rate concomitant with control animals or as outright weight loss. Thus, administration of activated CD4(+) T cells specific for the pancreatic enzyme amylase can induce pancreatitis in the rat in a manner that is reminiscent of human AIP.
Davidson
Todd S
TS
Department of Pathology, Dartmouth Medical School, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.
Longnecker
Daniel S
DS
Hickey
William F
WF
D019264:Adoptive Transfer; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001327:Autoimmune Diseases / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation; D009504:Neutrophils / Q000378:metabolism; D010195:Pancreatitis / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew
D000681:Amylases; D002256:Carbonic Anhydrases
Am J Gastroenterol. 2003 Dec;98(12):2811-2
14687846
Am J Gastroenterol. 2003 Dec;98(12):2694-9
14687819
Biochim Biophys Acta. 1975 Oct 22;403(2):456-60
810167
J Exp Med. 1977 Nov 1;146(5):1323-31
72777
J Histochem Cytochem. 1979 Jun;27(6):1029-34
110872
Cell. 1980 Aug;21(1):179-87
6157477
Science. 1989 Aug 18;245(4919):749-52
2788921
Am J Pathol. 1995 Sep;147(3):845-57
7545875
Ann Acad Med Singapore. 1999 Jan;28(1):133-40
10374039
Virchows Arch. 2004 Dec;445(6):552-63
15517359
J Autoimmun. 2000 Nov;15(3):359-67
11040076
Lab Invest. 2002 Apr;82(4):411-24
11950899
ScientificWorldJournal. 2002 Jun 11;2:1560-8
12806141
Pancreas. 2003 Jul;27(1):1-13
12826899
Pancreas. 2003 Jul;27(1):14-9
12826900
J Gastroenterol. 2003;38(10):982-4
14614606
Lab Invest. 2004 Mar;84(3):307-19
14767482