1997 Fiscal Year Final Research Report Summary
The immunopathogenesis and the regulation of hepatic lesions in murine model of primary biliary cirrhosis.
| Project/Area Number |
08457160
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
TANAKA Naomi Institute of Clinical Medicine, University of Tsukuba Professor, 臨床医学系, 教授 (60111530)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUZAKI Yasushi Institute of Clinical Medicine, University of Tsukuba, 臨床医学系, 講師 (50209532)
FUHJIWARA Michio University of Tokyo (80012722)
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| Project Period (FY) |
1996 – 1997
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| Keywords | primary biliary cirrhosis / graft versus host reaction / helper T cell subset / cytokine / interleukin-l0 / Interferon-gamma / adhesion molecule / VLA-4 |
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| Research Abstract |
We have previously reported that CD4^+ T cells induced primary biliary cirrhosis (PBC) Iike hepatic lesions in mice with graft-versus-host reaction (GVHR) due to major histocompatibility complex (MHC) class [[disparity. In this srudy, to ciarify the relationship between the cytokine profile produced by CD4^+ T cells and the formation of hepatic lesions. we sorted CD4^+ T cells from the liver using flowcytometer and examined their cytokine mRNA expressions at various time points after GVHR induction. Furthermore, we examined wheather Th1/Th2 balance might change during the suppression of lesions by antibodies against adhesion molecules. l) Histologically, the infiltration of CD4^+ T cells around the bile ducts was observed from day 5, and the lesions deteriorated gradually untii day 14. On day 14, CD8^-, B220^+ and Mac-l^+ cells, as well as CD4^+ T cells around the bile ducts were seen. In the liver infiltrating CD4^- T cells. the expression level of Th1 cytokine IFN-gamma mRNA was obse
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rved to increae at an early phase day 3, whereas that of Th2 cytokine IL-l0 mRNA was elevated at a later phase day 14. Serum levels of AMA on day 14 were significantly higher than that on day 5.2) H.E.staining showed the grade of portal cellular infiltration both in groups administered anti-VLA-4 antibodies and anti-VCAM-1 antibodies and only anti-VLA-4 antibodies were significantly suppressed compared to the control adminstered normal rat lgG.The induction of GVHR and the elevation of AMA were not alterd in these groups by administering monoclonal antibodies. The expressions of IL-2, IFNgamma, IL-4 and IL-l0 mRNA were not changed in these groups. Immunohistochemically, CD4, CD8, B220 or Mac-1 positive cells were detected in these groups. The elevation of IFN-gamma mRNA expression in the early phase before the appearance of NSDC lesions suggest that Th1 cells may be related to the pathogenesis of PBC in this model. Delayd expression of IL-l0 mRNA may reflect the suppression of cytokine production by Th1 cells in the liver. Moreover, the portal cellular infiltration in PBC animal model Is reduced by the administration of antibodies against VLA-4. However, cytokine profile of liver infiltrating Thyl.2^+CD4^+ lymphocytes and the composition of infiltrating cells were not changed. These results suggest that the administration of antibodies against adhision molecule may suppress PBC Iike lesions without Th1/Th2 balance. Less
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[Publications] Kimura T,Suzuki K,Inada S,Hayashi A,Saito H,Miyai T,Ohsugi Y,Matsuzaki Y,Tanaka N,Osuga T,Fujiwara M: "Indication of autoimmune disease by graft-versus-host reaction across MHC class II difference : modification of the lesions in IL-6 transgenic mice" Clin Exp Immunol. 95 (4). 525-529 (1994)
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