TY - JOUR
T1 - Immune-mediated cholangiohepatitis in neonatally thymectomized mice
T2 - The role of T cells and analysis of T-cell receptor Vβ usage
AU - Aisaka, Yasuyuki
AU - Watanabe, Yasuyuki
AU - Kamiyasu, Masaya
AU - Masanaga, Toshiyuki
AU - Tsuji, Keiji
AU - Nakanishi, Toshio
AU - Kajiyama, Goro
AU - Gershwin, M. Eric
PY - 2000
Y1 - 2000
N2 - We have previously reported the induction of immune-mediated cholangiohepatitis following injection of a hybrid recombinant proteins containing the E2 of the pyruvate dehydrogenase (PDC-E2) and the branched-chain keto-acid dehydrogenase (BCOADC-E2) to neonatally thymectomized (Tx) A/J mice. Further, we demonstrated that intrahepatic infiltrating mononuclear cells could transfer pathology to other Tx mice. To further our observations, we examined intrahepatic infiltrating mononuclear cells by flow cytometry and used cell transfer experiments to identify the phenotype involved. Interestingly, following immunization of neonatally Tx A/J mice and immunization with the bihybrid molecule, the number of CD3+infiltrating mononuclear cells were significantly higher (77.8%) compared with the control group. There was a small although not significant increase among intrahepatic infiltrating mononuclear cells and splenic cells of Vβ 5.1,5.2+, Vβ7+and Vβ17+. In addition, Vβ14+cells accounted for 20.4% of the infiltrating T-cells (P<0.01 vs. the control group). In further experiments, CD3+, CD4+or CD8+cells were isolated and removed from intrahepatic infiltrating mononuclear cells and subpopulations of mononuclear cells transferred to Tx mice. Both CD3+CD4+cells and CD3+CD8+cells are required for development of the lesion, and the damage is mediated by CD3+Vβ14+cells. (C) 2000 Academic Press.
AB - We have previously reported the induction of immune-mediated cholangiohepatitis following injection of a hybrid recombinant proteins containing the E2 of the pyruvate dehydrogenase (PDC-E2) and the branched-chain keto-acid dehydrogenase (BCOADC-E2) to neonatally thymectomized (Tx) A/J mice. Further, we demonstrated that intrahepatic infiltrating mononuclear cells could transfer pathology to other Tx mice. To further our observations, we examined intrahepatic infiltrating mononuclear cells by flow cytometry and used cell transfer experiments to identify the phenotype involved. Interestingly, following immunization of neonatally Tx A/J mice and immunization with the bihybrid molecule, the number of CD3+infiltrating mononuclear cells were significantly higher (77.8%) compared with the control group. There was a small although not significant increase among intrahepatic infiltrating mononuclear cells and splenic cells of Vβ 5.1,5.2+, Vβ7+and Vβ17+. In addition, Vβ14+cells accounted for 20.4% of the infiltrating T-cells (P<0.01 vs. the control group). In further experiments, CD3+, CD4+or CD8+cells were isolated and removed from intrahepatic infiltrating mononuclear cells and subpopulations of mononuclear cells transferred to Tx mice. Both CD3+CD4+cells and CD3+CD8+cells are required for development of the lesion, and the damage is mediated by CD3+Vβ14+cells. (C) 2000 Academic Press.
KW - Autoimmune cholangitis
KW - Bile duct
KW - Primary biliary cirrhosis
KW - T cell receptor
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U2 - 10.1006/jaut.2000.0368
DO - 10.1006/jaut.2000.0368
M3 - Article
C2 - 10756086
AN - SCOPUS:0033864408
VL - 14
SP - 239
EP - 246
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 3
ER -