肾移植排斥与 B 细胞、调节性 T 细胞和分化的 CD28-CD8+T 细胞失衡有关：对 1095 例移植活检的队列分析。
Kidney allograft rejection is associated with an imbalance of B cells, regulatory T cells and differentiated CD28-CD8+ T cells: analysis of a cohort of 1095 graft biopsies.
机构信息
Centre Hospitalier Universitaire (CHU) Nantes, Nantes Université, Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Research in Transplantation and Translational Immunology, Unité mixte de recherche (UMR) 1064, Institut de Transplantation Urologie-Néphrologie (ITUN), Nantes, France.
Laboratoire d'Immunologie, Centre d'ImmunoMonitorage Nantes-Atlantique (CIMNA), CHU Nantes, Nantes, France.
出版信息
Front Immunol. 2023 Apr 24;14:1151127. doi: 10.3389/fimmu.2023.1151127. eCollection 2023.
INTRODUCTION
The human immune system contains cells with either effector/memory or regulatory functions. Besides the well-established CD4+CD25hiCD127lo regulatory T cells (Tregs), we and others have shown that B cells can also have regulatory functions since their frequency and number are increased in kidney graft tolerance and B cell depletion as induction therapy may lead to acute rejection. On the other hand, we have shown that CD28-CD8+ T cells represent a subpopulation with potent effector/memory functions. In the current study, we tested the hypothesis that kidney allograft rejection may be linked to an imbalance of effector/memory and regulatory immune cells.
METHODS
Based on a large cohort of more than 1000 kidney graft biopsies with concomitant peripheral blood lymphocyte phenotyping, we investigated the association between kidney graft rejection and the percentage and absolute number of circulating B cells, Tregs, as well as the ratio of B cells to CD28-CD8+ T cells and the ratio of CD28-CD8+ T cells to Tregs. Kidney graft biopsies were interpreted according to the Banff classification and divided into 5 biopsies groups: 1) normal/subnormal, 2) interstitial fibrosis and tubular atrophy grade 2/3 (IFTA), 3) antibody-mediated rejection (ABMR), 4) T cell mediated-rejection (TCMR), and 5) borderline rejection. We compared group 1 with the other groups as well as with a combined group 3, 4, and 5 (rejection of all types) using multivariable linear mixed models.
RESULTS AND DISCUSSION
We found that compared to normal/subnormal biopsies, rejection of all types was marginally associated with a decrease in the percentage of circulating B cells (p=0.06) and significantly associated with an increase in the ratio of CD28-CD8+ T cells to Tregs (p=0.01). Moreover, ABMR, TCMR (p=0.007), and rejection of all types (p=0.0003) were significantly associated with a decrease in the ratio of B cells to CD28-CD8+ T cells compared to normal/subnormal biopsies. Taken together, our results show that kidney allograft rejection is associated with an imbalance between immune cells with effector/memory functions and those with regulatory properties.
简介
人体免疫系统包含具有效应/记忆或调节功能的细胞。除了已确立的 CD4+CD25hiCD127lo 调节性 T 细胞（Tregs）之外，我们和其他人已经表明，B 细胞也可以具有调节功能，因为它们的频率和数量在肾移植耐受和 B 细胞耗竭诱导治疗中增加，可能导致急性排斥反应。另一方面，我们已经表明，CD28-CD8+T 细胞代表具有强大效应/记忆功能的亚群。在当前的研究中，我们检验了这样一个假设，即肾移植排斥可能与效应/记忆和调节性免疫细胞的失衡有关。
方法
基于超过 1000 例肾移植活检的大型队列，以及伴随的外周血淋巴细胞表型，我们研究了循环 B 细胞、Tregs 的百分比和绝对数量与肾移植排斥之间的关联，以及 B 细胞与 CD28-CD8+T 细胞的比例和 CD28-CD8+T 细胞与 Tregs 的比例。根据 Banff 分类对肾移植活检进行解释，并将其分为 5 个活检组：1）正常/异常，2）间质纤维化和肾小管萎缩 2/3 级（IFTA），3）抗体介导的排斥反应（ABMR），4）T 细胞介导的排斥反应（TCMR），5）边界性排斥。我们将第 1 组与其他组以及第 3、4 和 5 组（所有类型的排斥）进行比较，使用多变量线性混合模型。
结果与讨论
我们发现，与正常/异常活检相比，所有类型的排斥反应与循环 B 细胞百分比的降低（p=0.06）略有相关，与 CD28-CD8+T 细胞与 Tregs 的比例升高（p=0.01）显著相关。此外，ABMR、TCMR（p=0.007）和所有类型的排斥反应（p=0.0003）与正常/异常活检相比，B 细胞与 CD28-CD8+T 细胞的比例降低显著相关。综上所述，我们的结果表明，肾移植排斥与具有效应/记忆功能和调节特性的免疫细胞之间的失衡有关。
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