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主要组织相容性复合体(MHC)和非MHC基因对小鼠心脏同种异体移植排斥反应性质的影响。I. 供体组织中单核细胞浸润及MHC I类/II类表达的动力学分析

The influence of MHC and non-MHC genes on the nature of murine cardiac allograft rejection. I. Kinetic analysis of mononuclear cell infiltrate and MHC-class I/class II expression in donor tissue.

作者信息

Wang Y C, Mayne A, Sell K W, Ahmed-Ansari A

机构信息

Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322.

出版信息

Transplantation. 1990 Aug;50(2):313-24. doi: 10.1097/00007890-199008000-00028.

DOI:10.1097/00007890-199008000-00028
PMID:2200176
Abstract

While normal cardiac tissue expresses low levels of MHC-class I, undetectable levels of MHC-class II antigens, and no mononuclear cell infiltrates, posttransplantation allogeneic donor cardiac tissue demonstrates dramatic increases of MHC-class I/class II expression coincident with the infiltration of the tissue with mononuclear cells. Results of this study demonstrate that the kinetics of MHC-class I/II antigen expression and the phenotype of mononuclear cell infiltrate are influenced, to a great degree, by the genetic H-2, intra-H-2 and non-H-2 incompatibility between donor and recipient strains of mice. Increases of MHC-class I precede class II expression in cells from donor cardiac tissue from completely allogeneic BALB/c, H-2-disparate B10.D2, B10.BR, and K, I-A and I-E-disparate B10.T (6R) strains of mice implanted in B10 recipients. In contrast, increase in the level of MHC-class II precedes MHC-class I increases in donor cardiac tissue from H-2-identical but non-H-2-incompatible A. By and the I-E + H-2D end-different B10.A(5R) donor tissue. The completely allogeneic, H-2-disparate or K, I-A, I-E-disparate donor cardiac tissue induced the infiltration of predominantly CD8+ T cells, whereas the non H-2 and I-E + H-2D end-different donor cardiac tissue induced the infiltration of predominantly CD4+ T cells. Finally, whereas bm1 donor cardiac tissue is rejected by B6 recipients by day 32, the (bm1 x bm12)F1 allografts are rejected by day 20, and both express MHC-class I antigens followed by MHC-class II antigens, and contain predominantly CD8+ T cells. In contrast, bm12 allografts are not rejected by B6 recipients, express chronic low levels of both MHC-class I and II antigens, and contain predominantly CD4+ T cells. Of interest is our preliminary finding that bm12 allografts placed in one ear of B6 recipients appear to modify the kinetics of MHC antigen expression and the predominant phenotype of mononuclear cell infiltrates in bm1 allografts placed in the opposite ear. Cumulatively, these data suggest that the type of genetic disparity between cardiac donor and recipient greatly influences the quantitative and qualitative host responses.

摘要

正常心脏组织表达低水平的MHC - I类分子,无法检测到MHC - II类抗原,且无单核细胞浸润,而移植后的同种异体供体心脏组织显示MHC - I类/MHC - II类表达显著增加,同时伴有单核细胞浸润。本研究结果表明,MHC - I类/II类抗原表达的动力学以及单核细胞浸润的表型在很大程度上受小鼠供体和受体品系之间的遗传H - 2、H - 2内和非H - 2不相容性影响。在植入B10受体的完全同种异体BALB/c、H - 2不同的B10.D2、B10.BR以及K、I - A和I - E不同的B10.T(6R)小鼠品系的供体心脏组织细胞中,MHC - I类分子的增加先于MHC - II类分子的表达。相反,在H - 2相同但非H - 2不相容的A和I - E + H - 2D末端不同的B10.A(5R)供体组织的心脏组织中,MHC - II类分子水平的增加先于MHC - I类分子的增加。完全同种异体、H - 2不同或K、I - A、I - E不同的供体心脏组织诱导主要是CD8 + T细胞浸润,而非H - 2和I - E + H - 2D末端不同的供体心脏组织诱导主要是CD4 + T细胞浸润。最后,虽然bm1供体心脏组织在第32天时被B6受体排斥,(bm1×bm12)F1同种异体移植物在第20天时被排斥,两者均先表达MHC - I类抗原,随后表达MHC - II类抗原,且主要含有CD8 + T细胞。相反,bm12同种异体移植物未被B6受体排斥,持续表达低水平的MHC - I类和II类抗原,且主要含有CD4 + T细胞。有趣的是,我们的初步发现是,置于B6受体一只耳朵的bm12同种异体移植物似乎改变了置于另一只耳朵的bm1同种异体移植物中MHC抗原表达的动力学以及单核细胞浸润的主要表型。总的来说,这些数据表明心脏供体和受体之间遗传差异的类型极大地影响宿主反应的数量和质量。

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