A ROLE FOR CD4+ T-CELLS IN THE PATHOGENESIS OF SKIN FIBROSIS IN TIGHT-SKIN MICE
A ROLE FOR CD4+ T-CELLS IN THE PATHOGENESIS OF SKIN FIBROSIS IN TIGHT-SKIN MICE
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DOI：
10.1002/eji.1830240634
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发表时间：
1994-06-01
影响因子：
5.4
通讯作者：
PAIGE, CJ
中科院分区：
文献类型：
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作者：
WALLACE, VA;KONDO, S;PAIGE, CJ
紧皮（Tsk/+）小鼠代表遗传性纤维化的鼠模型，其与在人硬皮病中观察到的皮肤纤维化具有一些相似性。Tsk/+动物在某些内脏器官中显示结缔组织的改变。皮肤纤维化可以过继转移到正常受体与Tsk/+骨髓或脾细胞和老年Tsk/+动物发展自身抗体的拓扑异构酶，这表明在Tsk/+小鼠的发病机制可能是由自身免疫介导的。为了确定T细胞亚群在纤维化疾病发病机制中的作用，将Tsk/+小鼠与CD 4-和CD 8-缺陷（CD 4（-/-）和CD 8（-/-））小鼠繁殖。与Tsk/+ CD 4（+）CD 8（+）对照小鼠相比，Tsk/+ CD 4（-/-）小鼠的皮肤纤维化明显减少，细胞结构减少，仅轻度胶原蛋白紊乱，但血清抗拓扑异构酶活性水平与Tsk对照小鼠无差异。相反，Tsk/+ CD 8（-/-）小鼠在皮肤中表现出与Tsk/+对照相同的组织学，但血清抗拓扑异构酶活性水平显著降低。肺病理学，即肺气肿，不受CD 4或CD 8突变的影响。这些数据表明，只有一些Tsk突变的病理学效应是T细胞依赖性的，并且不同的T细胞亚群影响纤维化疾病的这种多器官模型中的不同参数。
The tight skin (Tsk/+) mouse represents a murine model of heritable fibrosis with some similarities to the skin fibrosis seen in human scleroderma. Tsk/+ animals display alterations in connective tissue in some internal organs. Skin fibrosis can be adoptively transferred to normal recipients with Tsk/+ bone marrow or spleen cells and older Tsk/+ animals develop autoantibodies against topoisomerase suggesting that some of the pathogenesis in the Tsk/+ mouse may be mediated by autoimmunity. To determine the role of T cell subsets in the pathogenesis of fibrotic disease, Tsk/+ mice were bred with CD4- and CD8-deficient (CD4(-/-) and CD8(-/-)) mice. Tsk/+ CD4(-/-) mice showed a marked reduction in skin fibrosis as well as decreased cellularity and only mild collagen disorganization as compared to Tsk/+ CD4(+) CD8(+) control mice yet did not differ from Tsk controls in the level of serum anti-topoisomerase activity. In contrast, Tsk/+ CD8(-/-) mice exhibited the same histology in the skin as Tsk/+ controls yet had significantly reduced levels of serum anti-topoisomerase activity. Lung pathology, i.e. emphysema, was unaffected by both the CD4 or CD8 mutations. These data show that only some of the pathological effects of the Tsk mutation are T cell dependent and that different T cell subsets affect different parameters in this multi-organ model of fibrotic disease.