Prospective Tracking of Donor-Reactive T-Cell Clones in the Circulation and Rejecting Human Kidney Allografts.
Prospective Tracking of Donor-Reactive T-Cell Clones in the Circulation and Rejecting Human Kidney Allografts.
复制标题
在循环中对供体反应性T细胞克隆的前瞻性跟踪并拒绝人类肾脏同种异体移植物。
DOI：
10.3389/fimmu.2021.750005
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发表时间：
2021
影响因子：
7.3
通讯作者：
Oberbauer R
中科院分区：
文献类型：
--
作者：
Aschauer C;Jelencsics K;Hu K;Heinzel A;Gregorich MG;Vetter J;Schaller S;Winkler SM;Weinberger J;Pimenov L;Gualdoni GA;Eder M;Kainz A;Troescher AR;Regele H;Reindl-Schwaighofer R;Wekerle T;Huppa JB;Sykes M;Oberbauer R
异基因多肽和人类白细胞抗原分子的抗原识别导致移植后供者反应性T细胞的激活，可能导致T细胞介导的排斥反应(TCMR)。T细胞受体(TCR)谱系的测序可用于追踪肾移植后患者血液和组织中的供体反应谱系。在这项前瞻性队列研究中，117名抗CD25抗体诱导的非致敏肾移植受者包括在内。移植前和手术或适应症活检时采集外周血单个核细胞(PBMC)和移植物组织。在供体刺激混合淋巴细胞反应后进行TCRbeta链CDR3区的下一代测序(NGS)，以确定供体-反应性TCR谱系。6名接受TCMR的患者和6名接受常规活组织检查的无排斥反应的患者的血液和组织被询问是否有这些TCR。为了阐明T细胞克隆型的共同特征，对TCR谱系进行了网络分析。移植后，供者反应性CD4T细胞占全部细胞的比例从0.86±0.40%显著增加到2.06±0.40%(P<；0.001，平均差：-1.197，CI：-1.802，-0.593)。循环中供者反应性CD_4克隆型由0.72±0.33%增加到1.89±0.33%(P<；0.001，平均差：-1.168，CI：-1.724，-0.612)。在接受TCMR的受试者和对照组之间，移植活检时循环中供者反应性T细胞的百分比没有发现差异[p=0.64(CD4+)，p=0.52(CD8+)]。与同一时间的血液相比，移植物浸润性T细胞的供者反应性T细胞克隆型增加了6倍(3.7比0.6%和2.4比1.5%)，但是浸润性的TCR谱系没有被循环TCR谱系的组成反映出来，尽管有一些重叠。网络分析显示，供体-反应谱系的明显分离比血液中整体TCR谱系具有更高的模块化。这些发现表明，不同的T细胞克隆针对同种异体移植物中发现的许多非自身抗原而进行了一种未经编排的过程。在TCMR期间，供者反应性T细胞在移植肾中丰富，在血液中也发现了占优势的组织克隆。临床试验：nct：03422224()。
Antigen recognition of allo-peptides and HLA molecules leads to the activation of donor-reactive T-cells following transplantation, potentially causing T-cell-mediated rejection (TCMR). Sequencing of the T-cell receptor (TCR) repertoire can be used to track the donor-reactive repertoire in blood and tissue of patients after kidney transplantation. In this prospective cohort study, 117 non-sensitized kidney transplant recipients with anti-CD25 induction were included. Peripheral mononuclear cells (PBMCs) were sampled pre-transplant and at the time of protocol or indication biopsies together with graft tissue. Next-generation sequencing (NGS) of the CDR3 region of the TCRbeta chain was performed after donor stimulation in mixed lymphocyte reactions to define the donor-reactive TCR repertoire. Blood and tissue of six patients experiencing a TCMR and six patients without rejection on protocol biopsies were interrogated for these TCRs. To elucidate common features of T-cell clonotypes, a network analysis of the TCR repertoires was performed. After transplantation, the frequency of circulating donor-reactive CD4 T-cells increased significantly from 0.86 ± 0.40% to 2.06 ± 0.40% of all CD4 cells (p < 0.001, mean dif.: -1.197, CI: -1.802, -0.593). The number of circulating donor-reactive CD4 clonotypes increased from 0.72 ± 0.33% to 1.89 ± 0.33% (p < 0.001, mean dif.: -1.168, CI: -1.724, -0.612). No difference in the percentage of donor-reactive T-cells in the circulation at transplant biopsy was found between subjects experiencing a TCMR and the control group [p = 0.64 (CD4+), p = 0.52 (CD8+)]. Graft-infiltrating T-cells showed an up to six-fold increase of donor-reactive T-cell clonotypes compared to the blood at the same time (3.7 vs. 0.6% and 2.4 vs. 1.5%), but the infiltrating TCR repertoire was not reflected by the composition of the circulating TCR repertoire despite some overlap. Network analysis showed a distinct segregation of the donor-reactive repertoire with higher modularity than the overall TCR repertoire in the blood. These findings indicate an unchoreographed process of diverse T-cell clones directed against numerous non-self antigens found in the allograft. Donor-reactive T-cells are enriched in the kidney allograft during a TCMR episode, and dominant tissue clones are also found in the blood. Clinicaltrials.gov: NCT: 03422224 ().
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影响因子：
17.1
作者：
Morris H;DeWolf S;Robins H;Sprangers B;LoCascio SA;Shonts BA;Kawai T;Wong W;Yang S;Zuber J;Shen Y;Sykes M
通讯作者：
Sykes M
影响因子：
8.8
作者：
Dziubianau, M.;Hecht, J.;Babel, N.
通讯作者：
Babel, N.
DOI：
10.1073/pnas.1809642115
发表时间：
2018-12-11
影响因子：
11.1
作者：
Pogorelyy, Mikhail V.;Minervina, Anastasia A.;Lebedev, Yuri B.
通讯作者：
Lebedev, Yuri B.
影响因子：
48
作者：
Shugay, Mikhail;Britanova, Olga V.;Chudakov, Dmitriy M.
通讯作者：
Chudakov, Dmitriy M.
影响因子：
5.4
作者：
Fischer, Michaela;Leyking, Sarah;Sester, Urban
通讯作者：
Sester, Urban