Alloantibody- and T cell-mediated immunity in the pathogenesis of transplant arteriosclerosis: lack of progression to sclerotic lesions in B cell-deficient mice.
Alloantibody- and T cell-mediated immunity in the pathogenesis of transplant arteriosclerosis: lack of progression to sclerotic lesions in B cell-deficient mice.
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移植动脉硬化发病机制中同种抗体和 T 细胞介导的免疫：B 细胞缺陷小鼠中缺乏进展为硬化病变。
DOI：
10.1097/00007890-199712150-00005
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发表时间：
1997
期刊：
影响因子：
6.2
通讯作者：
Colvin,RB
中科院分区：
文献类型：
--
作者：
Russell,PS;Chase,CM;Colvin,RB
背景：体液免疫和细胞免疫在慢性移植物动脉病发生中的相对作用已经被考虑了几年。我们通过在选定的小鼠品系之间进行心脏移植来寻找关于这些问题的确凿证据，以分离每种形式的免疫反应的影响。BR心脏移植给缺乏免疫球蛋白(μMT)的B细胞缺陷受体。将它们的血管与相同遗传背景(C57BL/6)的完全反应性受体的移植血管进行比较。其他证据来自其他菌株组合的比较。结果：移植给B细胞缺陷和正常受体的患者发生了细胞性冠状动脉内皮炎，动脉中层遭到破坏，并伴有T淋巴细胞和巨噬细胞与内皮表面的粘连。在B细胞缺陷受体中，与完全反应性C57BL/6受体相比，无向心性迁移的平滑肌、α肌动蛋白阳性的肌内膜细胞和极少的胶原或基质沉积。在另外两种供体-受者组合中，抗供体抗体通常是检测不到的(B10。BR→B10。A和12 9→C57BL/6)，内膜纤维化少见。然而，B10。受者能够在B10中产生纤维性病变。BR心脏给予抗供体，I类抗体通过被动转移，正如我们以前在SCID受者中观察到的那样。结论：综合而言，这些发现表明，内皮炎是抗体非依赖性的，而抗体可以加强，并足以治疗充分发展的纤维性、慢性移植物血管病变。控制慢性病变的治疗策略必须考虑抑制体液反应。
Background.The relative roles of humoral and cell-mediated immunity in generating chronic allograft arteriopathy have been considered for several years. We have sought definitive evidence regarding these questions using heart transplants between mouse strains selected to isolate the effects of each form of immune responsiveness.Methods.B10. BR hearts were transplanted to B cell-deficient recipients that are devoid of immunoglobulins (μMT). Their vessels were compared with those of transplants to fully reactive recipients of the same genetic background (C57BL/6). Additional evidence came from comparisons in other strain combinations.Results.Transplants to B cell-deficient and normal recipients developed cellular coronary endothelialitis, with destruction of the arterial media, accompanied by the adherence of T lymphocytes and macrophages to endothelial surfaces. In B cell-deficient recipients, there was no centripetal migration of smooth muscle, α-actin-positive myointimal cells and little deposition of collagen or ground substance, compared with lesions in fully reactive C57BL/6 recipients in which these changes are prominent. In two other donor-recipient combinations in which anti-donor antibodies are generally undetectable (B10. BR→ B10. A and 129→ C57BL/6), intimal fibrosis was uncommon. However, B10. A recipients became capable of producing fibrous lesions in B10. BR hearts when given anti-donor, class I antibody by passive transfer, as we have observed previously in scid recipients.Conclusions.Taken together, these findings indicate that endothelialitis is antibody-independent, whereas antibodies potentiate and can be sufficient for fully developed, fibrous, chronic allograft vasculopathy. Therapeutic strategies for controlling chronic lesions must consider inhibition of the humoral response.