Department of Internal Medicine, Nephrology and Transplantation, Erasmus University Medical Center (Erasmus MC) Transplant Institute.
Department of Haematology, and.
JCI Insight. 2023 Nov 8;8(21):e172681. doi: 10.1172/jci.insight.172681.
Tissue-resident lymphocytes (TRLs) are critical for local protection against viral pathogens in peripheral tissue. However, it is unclear if TRLs perform a similar role in transplanted organs under chronic immunosuppressed conditions. In this study, we aimed to characterize the TRL compartment in human kidney transplant nephrectomies and examine its potential role in antiviral immunity. The TRL compartment of kidney transplants contained diverse innate, innate-like, and adaptive TRL populations expressing the canonical residency markers CD69, CD103, and CD49a. Chimerism of donor and recipient cells was present in 43% of kidney transplants and occurred in all TRL subpopulations. Paired single-cell transcriptome and T cell receptor (TCR) sequencing showed that donor and recipient tissue-resident memory T (TRM) cells exhibit striking similarities in their transcriptomic profiles and share numerous TCR clonotypes predicted to target viral pathogens. Virus dextramer staining further confirmed that CD8 TRM cells of both donor and recipient origin express TCRs with specificities against common viruses, including CMV, EBV, BK polyomavirus, and influenza A. Overall, the study results demonstrate that a diverse population of TRLs resides in kidney transplants and offer compelling evidence that TRM cells of both donor and recipient origin reside within this TRL population and may contribute to local protection against viral pathogens.
组织驻留淋巴细胞 (TRL) 对于外周组织中病毒病原体的局部保护至关重要。然而,在慢性免疫抑制条件下,TRL 在移植器官中是否发挥类似作用尚不清楚。在这项研究中,我们旨在描述人类肾移植肾切除标本中的 TRL 区室,并研究其在抗病毒免疫中的潜在作用。肾移植的 TRL 区室包含多种先天、先天样和适应性 TRL 群体,表达经典的驻留标志物 CD69、CD103 和 CD49a。供体和受体细胞的嵌合存在于 43%的肾移植中,并且发生在所有 TRL 亚群中。配对的单细胞转录组和 T 细胞受体 (TCR) 测序表明,供体和受体组织驻留记忆 T (TRM) 细胞在转录组谱上具有惊人的相似性,并共享许多预测针对病毒病原体的 TCR 克隆型。病毒 dextramer 染色进一步证实,供体和受体来源的 CD8 TRM 细胞均表达针对常见病毒(包括 CMV、EBV、BK 多瘤病毒和流感 A)的 TCR,具有特异性。总的来说,研究结果表明,多样化的 TRL 群体存在于肾移植中,并提供了令人信服的证据,即供体和受体来源的 TRM 细胞存在于该 TRL 群体中,并可能有助于针对病毒病原体的局部保护。