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

慢性GvHR和gvhd小鼠模型得到如下结果：用亲代淋巴样细胞接种F1杂交小鼠诱导慢性GvHR。选择仅H-2I区和S区不同的同源重组菌株ATL和ATH联合诱导ii类gvhr。移植物CD4^+ T细胞对伴侣异体抗原的选择性激活是GvHR的主要事件，然后导致移植物和宿主细胞的伴随激活。特别是在不同MHC抗原的菌株组合中，即DBA/2* (C57BL/6xDBA/2) F1或BALB/c* (BALB/cxA/J) F1，特异性地观察到移植物CD4^+细胞的优先而非选择性活化。导致这一现象的因素是移植物CD8^+ T细胞对同种异体I类MHC抗原的低反应性和宿主CD8细胞在D2-GvHR情况下的抗dba /2活性。慢性gvh -脾中以CD4细胞活化为主，CD4/CD8比值始终为bb0 1.2。GvHR第2周胸腺出现中度萎缩。凋亡细胞频率增加，S期细胞减少是导致其萎缩的细胞事件。虽然不像急性GvHR那么明显，但由于慢性和急性GvHR的早期萎缩过程基本相同，发生了细胞改变。非化脓性破坏性胆管炎是慢性GvH病的一种肝脏病变。其特点是早在GvHR第2天，门管区淋巴细胞和上皮内浸润，上皮膜上强烈表达MHC II类抗原。现场产生的干扰素γ是诱发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.