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分析 T 细胞同种异体抗原反应 供体特异性抗体的肾移植受者的直接途径。

Analysis of T-cell alloantigen response a direct pathway in kidney transplant recipients with donor-specific antibodies.

机构信息

Department of Urology, Hokkaido University Hospital, Sapporo, Japan.

Division of Renal Surgery and Transplantation, Jichi Medical University, Shimotsuke, Tochigi, Japan.

出版信息

Front Immunol. 2023 May 3;14:1164794. doi: 10.3389/fimmu.2023.1164794. eCollection 2023.

DOI:10.3389/fimmu.2023.1164794
PMID:37207202
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10189043/
Abstract

Donor-specific antibodies (DSAs) are the main cause of graft loss over time. The direct pathway of alloantigen recognition is important in the pathogenesis of acute rejection. Recent studies have suggested that the direct pathway also contributes to the pathogenesis of chronic injury. Nevertheless, there are no reports on T-cell alloantigen response the direct pathway in kidney recipients with DSAs. We analyzed the T-cell alloantigen response the direct pathway in kidney recipients with DSAs (DSA+) or without DSAs (DSA-). A mixed lymphocyte reaction assay was implemented to assess the direct pathway response. DSA+ patients showed significantly higher CD8 and CD4 T cell responses to donor cells than DSA- patients. Furthermore, proliferating CD4 T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA- patients. In a comparison between anti-donor and third-party responses, the anti-donor CD8 and CD4 T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues the direct alloantigen recognition pathway. These data contribute to an understanding of DSAs pathogenicity during kidney transplantation.

摘要

供体特异性抗体(DSA)是导致移植物随时间丢失的主要原因。同种异体抗原识别的直接途径在急性排斥反应的发病机制中很重要。最近的研究表明,直接途径也有助于慢性损伤的发病机制。然而,目前尚无关于 DSA 肾移植受者中 T 细胞同种异体抗原反应直接途径的报道。我们分析了 DSA(DSA+)或无 DSA(DSA-)肾移植受者的 T 细胞同种异体抗原反应直接途径。实施混合淋巴细胞反应测定来评估直接途径反应。DSA+患者对供体细胞的 CD8 和 CD4 T 细胞反应明显高于 DSA-患者。此外,与 DSA-患者相比,增殖的 CD4 T 细胞在 DSA+患者中表现出 Th1 和 Th17 反应的明显增加。在与抗供体和第三方反应的比较中,抗供体 CD8 和 CD4 T 细胞反应明显低于抗第三方反应。相比之下,DSA+患者不存在供体特异性低反应性。我们的研究表明,DSA+受者对供体组织具有更强的免疫反应潜力,即直接同种抗原识别途径。这些数据有助于理解 DSAs 在肾移植过程中的致病性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d52/10189043/646503a28162/fimmu-14-1164794-g007.jpg
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Donor-specific hypo-responsiveness occurs in simultaneous liver-kidney transplant recipients after the first year.供者特异性低反应性在肝-肾联合移植受者中于第 1 年后出现。
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Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation.移植后,引发同种异体反应性T细胞反应的是供体来源的外泌体而非过客白细胞。
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