Induction and persistence of immune-mediated cholangiohepatitis in neonatally thymectomized mice

Toshiyuki Masanaga, Yasuyuki Watanabe, Judith A Van de Water, Patrick S Leung, Toshio Nakanishi, Goro Kajiyama, Boris H. Ruebner, Ross L. Coppel, M. Eric Gershwin

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The availability of recombinant autoantigens allows the experimental study of the relationships between primary biliary cirrhosis (PBC) and mitochondrial antigens. We took advantage of these recombinant autoantigens and attempted to induce autoimmune cholangitis by immunizing neonatally thymectomized (NTx) lipopolysaccharide (LPS)-treated A/J mice, known to be prone to organ-specific autoimmune diseases. We employed a recombinant protein containing a dual-headed molecule that coexpresses the immunodominant epitope of the E2 subunits of the pyruvate dehydrogenase complex and the branched-chain ketoacid dehydrogenase complex. We report herein that an immune-mediated cholangiohepatitis was induced by such immunization and the concurrent injection of LPS into NTx mice. The incidence of cholangitis was 79% in the NTx, immunized, LPS group compared to 14% in the NTx, nonimmunized, LPS group. The histopathology ranged from mild to severe and included bile duct damage, focal hepatic necrosis, and endotheliitis, but no granulomas. Moreover, almost all such lesions persisted for 12 weeks after the discontinuation of immunization and LPS injections in the NTx mice. Interestingly, we were successful (89%) in transferring the cholangiohepatitis by injection of liver infiltrating mononuclear cells from the NTx, immunized, LPS mice into congenic nonimmunized NTx mice; such lesions could not be transferred with spleen cells. Although the pathology is not typical of PBC, this model offers a unique venue for the study of immune- mediated hepatobiliary injury.

Original languageEnglish (US)
Pages (from-to)141-149
Number of pages9
JournalClinical Immunology and Immunopathology
Volume89
Issue number2
DOIs
StatePublished - Nov 1998

Fingerprint

Lipopolysaccharides
Cholangitis
Biliary Liver Cirrhosis
Injections
Immunization
Dihydrolipoyllysine-Residue Acetyltransferase
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Congenic Mice
Immunodominant Epitopes
Liver
Autoantigens
Bile Ducts
Granuloma
Recombinant Proteins
Autoimmune Diseases
Necrosis
Spleen
Pathology
Antigens
Incidence

Keywords

  • Animal model
  • Autoimmune cholangitis
  • Bile duct
  • Primary biliary cirrhosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pathology and Forensic Medicine

Cite this

Induction and persistence of immune-mediated cholangiohepatitis in neonatally thymectomized mice. / Masanaga, Toshiyuki; Watanabe, Yasuyuki; Van de Water, Judith A; Leung, Patrick S; Nakanishi, Toshio; Kajiyama, Goro; Ruebner, Boris H.; Coppel, Ross L.; Gershwin, M. Eric.

In: Clinical Immunology and Immunopathology, Vol. 89, No. 2, 11.1998, p. 141-149.

Research output: Contribution to journalArticle

Masanaga, Toshiyuki ; Watanabe, Yasuyuki ; Van de Water, Judith A ; Leung, Patrick S ; Nakanishi, Toshio ; Kajiyama, Goro ; Ruebner, Boris H. ; Coppel, Ross L. ; Gershwin, M. Eric. / Induction and persistence of immune-mediated cholangiohepatitis in neonatally thymectomized mice. In: Clinical Immunology and Immunopathology. 1998 ; Vol. 89, No. 2. pp. 141-149.
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