1995 Fiscal Year Final Research Report Summary
In Situ Immunocytological and Molecular Pathological Analysis of the Lesions in the Target Organs of Chronic GvH Disease
| Project/Area Number |
06670225
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Shimane Medical University |
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Principal Investigator |
HARADA Takayuki Shimane Medical University, Department of Pathology, Professor, 医学部, 教授 (90112135)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Chronic GvH disease / T cell / Spleen / Thymus / Immunohistochemistry / Cytokine / Apoptosis / S phase cell |
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| Research Abstract |
Following results were obtained using mouse models of chronic GvHR and GvHD.
1.Chronic GvHR was induced by inoculating parental lymphoid cells into F1 hybrid mouse. Combination of ATL and ATH,which were congenic recombinant strains differing only in H-2I and S region from each other, was chosen to induce class II-GvHR.Selective activation against partner's alloantigen of graft CD4^+ T cells was the primary event of the GvHR and then led to concomitant activation of both graft and host cells. In particular combinations of strains differing whole MHC antigens, namely, DBA/2* (C57BL/6xDBA/2) F1 or BALB/c* (BALB/cxA/J) F1, preferential but not selective activation of graft CD4^+ cells was characteristically observed. Contributing factors to this phenomenon were low responsiveness of graft CD8^+ T cells to allogeneic class I MHC antigens and anti-DBA/2 activity of host CD8 cells in the case of D2-GvHR.Predominant activation of CD4 cells in the chronic GvH-spleen was expressed as the ratio of CD4/CD8 was always >1.
2.Moderate atrophy of the thymus was observed in the 2nd week of GvHR.Increase of the frequency of apoptotic cell and decrease of S phase cell were cellular event leading to its atrophy. Although it was not so obvious as acute GvHR,cellular change occurred as early process of atrophy was essentially same between chronic and acute GvHR's.
3.Non-suppurative destructive cholangitis was a liver lesion of chronic GvH disease. It was characterized by periductal and intraepithelial infiltration of lymphocyte in the portal area and strong expression of MHC class II antigen on the epithelial membrane as early as 2nd day of GvHR.Interferon-gamma produced in site was important factor to induce aberrant expression of the antigen.
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