Cross-reactivity of cytomegalovirus-specific CD8+ T cells to allo-major histocompatibility complex class I molecules
Cross-reactivity of cytomegalovirus-specific CD8+ T cells to allo-major histocompatibility complex class I molecules
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DOI：
10.1097/01.tp.0000131158.81346.64
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发表时间：
2004-06-27
期刊：
影响因子：
6.2
通讯作者：
Ten Berge, IJM
中科院分区：
文献类型：
--
作者：
Gamadia, LE;Remmerswaal, EB;Ten Berge, IJM
背景在移植环境中，巨细胞病毒（CMV）感染是一种常见的并发症。巨细胞病毒感染与实体器官移植中移植物排斥反应和骨髓移植中移植物抗宿主病的发生率较高相关。这种关联的潜在机制可能是CMV特异性CD 8（+）T细胞的产生，其能够分别与移植物和宿主上存在的同种异体抗原交叉反应。尽管迄今为止，还不能对针对同种异体主要组织相容性复合体（MHC）I类分子的CD 8（+）T细胞库进行直接的离体分析，但病毒特异性细胞可以通过使用MHC-肽四聚体复合体容易地计数。在这项研究中，作者使用这种技术通过用同种抗原刺激CMV特异性CD 8（+）T细胞来分析自身MHC-病毒肽和同种MHC复合物之间潜在的重叠CD 8（+）T细胞库。作者发现CMV特异性CD 8（+）T细胞在同种异体抗原刺激下活化并增殖。虽然这些细胞对CMV肽脉冲靶细胞具有细胞毒性，但未检测到CMV特异性细胞对同种异体抗原的细胞毒性，推断同种异体抗原刺激的病毒特异性CTL存在其他移植物损伤机制。
Background. In transplantation settings, cytomegalovirus (CMV) infection is a common complication. CMV infection is associated with a higher incidence of graft rejection in solid organ transplantation and graft-versus-host disease in bone marrow transplantation. The underlying mechanism of this association could be the generation of CMV-specific CD8(+) T cells capable of cross-reacting with alloantigens present on graft and host, respectively.Methods. Whereas as to date, no direct ex vivo analysis can be performed of the CD8(+) T-cell repertoire directed at allo-major histocompatibility complex (MHC) class I molecules, virus-specific cells can be readily enumerated by use of MHC-peptide tetrameric complexes. In this study, the authors used this technique to analyze potential overlapping CD8(+) T-cell repertoires between self-MHC-viral peptide and alloMHC complexes by stimulating CMV-specific CD8(+) T cells with alloantigens.Results. The authors found that CMV-specific CD8(+) T cells are activated and proliferate on stimulation with alloantigens.Conclusions. Although these cells are cytotoxic against CMV-peptide pulsed target cells, no cytotoxicity of CMV-specific cells to alloantigens could be detected, inferring that there are other mechanisms of graft damage by alloantigen-stimulated virus-specific CTL.