CD8temra cells showed strong and consistent association with graft failure, regardless of the Banff rejection phenotypes. Background The link between the histology of kidney transplant rejection, especially antibody-mediated rejection, T-cell–mediated rejection, and mixed rejection, and the types of infiltrating immune cells is currently not well charted. Cost and technical complexity of single-cell analysis hinder large-scale studies of the relationship between cell infiltrate profiles and histological heterogeneity. Methods In this cross-sectional study, we assessed the composition of nine intragraft immune cell types by using a validated kidney transplant–specific signature matrix for deconvolution of bulk transcriptomics in three different kidney transplant biopsy datasets (N=403, N=224, N=282). The association and discrimination of the immune cell types with the Banff histology and the association with graft failure were assessed individually and with multivariable models. Unsupervised clustering algorithms were applied on the overall immune cell composition and compared with the Banff phenotypes. Results Banff-defined rejection was related to high presence of CD8+ effector T cells, natural killer cells, monocytes/macrophages, and, to a lesser extent, B cells, whereas CD4+ memory T cells were lower in rejection compared with no rejection. Estimated intragraft effector memory–expressing CD45RA (TEMRA) CD8+ T cells were strongly and consistently associated with graft failure. The large heterogeneity in immune cell composition across rejection types prevented supervised and unsupervised methods to accurately recover the Banff phenotypes solely on the basis of immune cell estimates. The lack of correlation between immune cell composition and Banff-defined rejection types was validated using multiplex immunohistochemistry. Conclusions Although some specific cell types (FCGR3A+ myeloid cells, CD14+ monocytes/macrophages, and NK cells) partly discriminated between rejection phenotypes, the overall estimated immune cell composition of kidney transplants was ill-related to main Banff-defined rejection categories and added to the Banff lesion scoring and evaluation of rejection severity. The estimated intragraft CD8temra cells bore strong and consistent association with graft failure and were independent of Banff-grade rejection....

中文翻译：

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浸润免疫细胞组合物在肾移植排斥反应中的临床相关性


无论班夫排斥表型如何，CD8temra 细胞都显示出与移植失败的强烈且一致的相关性。背景 肾移植排斥反应（尤其是抗体介导的排斥反应、T 细胞介导的排斥反应和混合排斥反应）的组织学与浸润免疫细胞类型之间的联系目前尚未明确。单细胞分析的成本和技术复杂性阻碍了对细胞浸润特征与组织学异质性之间关系的大规模研究。方法在这项横断面研究中，我们使用经过验证的肾移植特异性特征矩阵对三个不同肾移植活检数据集中的批量转录组学进行解卷积，评估了九种移植物内免疫细胞类型的组成（N = 403、N = 224、N =282）。免疫细胞类型与班夫组织学的关联和区分以及与移植失败的关联均通过多变量模型进行单独评估。对整体免疫细胞组成应用无监督聚类算法，并与班夫表型进行比较。结果 Banff 定义的排斥与 CD8+ 效应 T 细胞、自然杀伤细胞、单核细胞/巨噬细胞以及较小程度的 B 细胞的大量存在有关，而与无排斥相比，CD4+ 记忆 T 细胞的排斥程度较低。估计移植物内效应记忆表达 CD45RA (TEMRA) CD8+ T 细胞与移植失败密切相关。不同排斥类型之间免疫细胞组成的巨大异质性阻碍了监督和非监督方法仅根据免疫细胞估计准确恢复班夫表型。 使用多重免疫组织化学验证了免疫细胞组成与班夫定义的排斥类型之间缺乏相关性。结论 尽管某些特定细胞类型（FCGR3A+ 骨髓细胞、CD14+ 单核细胞/巨噬细胞和 NK 细胞）在排斥表型之间存在部分区别，但肾移植的总体估计免疫细胞组成与班夫定义的主要排斥类别不相关，并添加到了排斥反应表型中。班夫病变评分和排斥严重程度评估。估计的移植物内 CD8temra 细胞与移植物失败具有强烈且一致的相关性，并且独立于班夫级排斥反应......