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 language | English (US) |
|---|---|
| Pages (from-to) | 141-149 |
| Number of pages | 9 |
| Journal | Clinical Immunology and Immunopathology |
| Volume | 89 |
| Issue number | 2 |
| DOIs | |
| State | Published - Nov 1998 |
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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 journal › Article
}
TY - JOUR
T1 - Induction and persistence of immune-mediated cholangiohepatitis in neonatally thymectomized mice
AU - Masanaga, Toshiyuki
AU - Watanabe, Yasuyuki
AU - Van de Water, Judith A
AU - Leung, Patrick S
AU - Nakanishi, Toshio
AU - Kajiyama, Goro
AU - Ruebner, Boris H.
AU - Coppel, Ross L.
AU - Gershwin, M. Eric
PY - 1998/11
Y1 - 1998/11
N2 - 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.
AB - 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.
KW - Animal model
KW - Autoimmune cholangitis
KW - Bile duct
KW - Primary biliary cirrhosis
UR - http://www.scopus.com/inward/record.url?scp=0031735754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031735754&partnerID=8YFLogxK
U2 - 10.1006/clin.1998.4599
DO - 10.1006/clin.1998.4599
M3 - Article
C2 - 9787116
AN - SCOPUS:0031735754
VL - 89
SP - 141
EP - 149
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
IS - 2
ER -