In Situ Immunocytological and Molecular Pathological Analysis of the Lesions in the Target Organs of Chronic GvH Disease

在慢性GvHR和GvHD小鼠模型上获得了以下结果：1.将亲代淋巴细胞接种F1杂交小鼠诱导慢性GvHR。ATL和ATH是仅在H-2I区和S区不同的同源重组菌株，它们联合诱导II类GvHR，选择性激活移植物CD4T细胞的同种异体抗原是GvHR的主要事件，继而导致移植物和宿主细胞的同时激活。在不同完整MHC抗原的菌株组合，即DBA/2*(C57BL/6xDBA/2)F1或BALB/c*(BALB/CXA/J)F1中，观察到移植物CD4细胞的优先激活而不是选择性激活。慢性GVH脾中CD_4细胞的活化主要表现为CD_4/CD_8比值始终为&GT；1.2胸腺轻度萎缩，细胞凋亡率增加和S时相细胞减少是导致其萎缩的细胞事件。虽然不像急性GvHR那样明显，但慢性GvHR和急性GvHR的早期萎缩过程基本相同。3.非化脓性破坏性胆管炎是慢性GVH病的一种肝损害。GvHR发病后第2天即可见汇管区淋巴管周围和上皮内淋巴细胞浸润，上皮膜MHC-II类抗原强阳性表达，局部产生的干扰素-γ是诱导该抗原异常表达的重要因素。

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.