Antibody-mediated rejection of single class I MHC-disparate cardiac allografts.

Antibody-mediated rejection of single class I MHC-disparate cardiac allografts.
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DOI:
10.1111/j.1600-6143.2012.04073.x
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发表时间:
2012-08
期刊:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子:
--
通讯作者:
Fairchild RL
Fairchild RL
中科院分区:
其他
文献类型:
--
作者:
Hattori Y;Bucy RP;Kubota Y;Baldwin WM 3rd;Fairchild RL

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小鼠CCR 5 −/−受体产生高滴度的抗体,以完成MHC不匹配的心脏和肾脏同种异体移植。为了研究I类MHC抗体介导的同种异体移植物损伤的机制,我们测试了野生型C57 BL/6(H-2b)和B6.CCR5−/−受体中转基因表达单一I类MHC差异的心脏同种异体移植物的排斥反应。CCR 5 −/−受体中的供体特异性抗体滴度比野生型受体高30倍。B6.Kd同种异体移植物在野生型受体中存活超过60天,而CCR 5 −/−受体在14天内排斥所有同种异体移植物。排斥反应伴随着CD 8 T细胞、中性粒细胞和巨噬细胞的浸润以及移植物毛细血管中的C4d沉积。B6.Kd同种异体移植物被CD 8 −/−/CCR 5 −/−排斥,但不被μMT−/−/CCR 5 −/−排斥,这表明受体需要抗体而不是CD 8 T细胞。在第10天从CCR 5-/-和CD 8-/-/CCR 5-/-受体以及注射抗Kd抗体的RAG-1-/-同种异体移植受体中取出的移植物表达高水平的穿孔素、髓过氧化物酶和CCL 5 mRNA。这些研究表明,抗供体I类MHC抗体的持续产生可以介导同种异体移植物排斥,供体反应性CD 8 T细胞与抗体协同作用以促进排斥,并且在排斥期间三种生物标志物的表达可以在不存在这种CD 8 T细胞活性的情况下发生。
Murine CCR5−/− recipients produce high titers of antibody to complete MHC-mismatched heart and renal allografts. To study mechanisms of class I MHC antibody-mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild-type C57BL/6 (H-2b) and B6.CCR5−/− recipients. Donor-specific antibody titers in CCR5−/− recipients were 30-fold higher than in wild-type recipients. B6.Kd allografts survived longer than 60 days in wild-type recipients whereas CCR5−/− recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils, and macrophages and C4d deposition in the graft capillaries. B6.Kd allografts were rejected by CD8−/−/CCR5−/−, but not μMT−/−/CCR5−/−, recipients indicating the need for antibody but not CD8 T cells. Grafts retrieved at day 10 from CCR5−/− and CD8−/−/CCR5−/− recipients and from RAG-1−/− allograft recipients injected with anti-Kd antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of anti-donor class I MHC antibody can mediate allograft rejection, that donor-reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity.
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期刊: TRANSPLANTATION
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发表时间: 2009-10
期刊: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子: --
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