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

本研究采用慢性GvHR和GvHD小鼠模型，获得以下结果：1.用亲代淋巴细胞诱导F1代小鼠产生慢性GvHR。选择仅H-2 I和S区不同的重组菌ATL和ATH组合诱导II类GvHR，GvHR的主要作用是选择性激活移植物CD 4 ^+ T细胞，然后导致移植物和宿主细胞同时激活。在不同MHC抗原的菌株组合中，即DBA/2*（C57 BL/6xDBA/2）F1或BALB/c*（BALB/cxA/J）F1，移植物CD 4 ^+细胞的优先激活而非选择性激活是典型的。D2-GvHR患者移植物CD 8 ^+ T细胞对同种异体I类MHC抗原的低反应性和宿主CD 8细胞的抗DBA/2活性是导致这一现象的因素。1.2.GvHR第2周胸腺出现中度萎缩，凋亡细胞增多和S期细胞减少是导致胸腺萎缩的细胞事件。慢性GvHR与急性GvHR的肝细胞萎缩早期过程基本相同，但不如急性GvHR明显。3.非化脓性破坏性胆管炎是慢性GvH病的一种肝脏病变。早在GvHR第2天，汇管区导管周和上皮内淋巴细胞浸润，上皮细胞膜上MHC-II类抗原表达增强，IFN-γ的产生是诱导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.