Alteration of γδ T cell subsets in non-human primates transplanted with GGTA1 gene-deficient porcine blood vessels.

IF 3.3 4区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL
Xenotransplantation Pub Date : 2024-01-01 Epub Date: 2023-12-19 DOI:10.1111/xen.12838
Sujin Lee, Yun Shin Chung, Kyo Won Lee, Miran Choi, Chung Hee Sonn, Won Jun Oh, Hun Gi Hong, Joohyun Shim, Kimyung Choi, Sung Joo Kim, Jae Berm Park, Tae Jin Kim
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引用次数: 0

Abstract

Background: αGal-deficient xenografts are protected from hyperacute rejection during xenotransplantation but are still rejected more rapidly than allografts. Despite studies showing the roles of non-Gal antibodies and αβ T cells in xenograft rejection, the involvement of γδ T cells in xenograft rejection has been limitedly investigated.

Methods: Six male cynomolgus monkeys were transplanted with porcine vessel xenografts from wild-type (n = 3) or GGTA1 knockout (n = 3) pigs. We measured the proportions and T cell receptor (TCR) repertoires of blood γδ T cells before and after xenotransplant. Grafted porcine vessel-infiltrating immune cells were visualized at the end of experiments.

Results: Blood γδ T cells expanded and infiltrated into the graft vessel adventitia following xenotransplantation of α-Gal-deficient pig blood vessels. Pre- and post-transplant analysis of γδ TCR repertoire revealed a transition in δ chain usage post-transplantation, with the expansion of several clonotypes of δ1, δ3, or δ7 chains. Furthermore, the distinctions between pre- and post-transplant δ chain usages were more prominent than those observed for γ chain usages.

Conclusion: γδ TCR repertoire was significantly altered by xenotransplantation, suggesting the role of γδ T cells in sustained xenoreactive immune responses.

移植了 GGTA1 基因缺陷猪血管的非人灵长类动物体内 γδ T 细胞亚群的变化。
背景:在异种移植过程中,αGal缺陷的异种移植物可避免超急性排斥反应,但其排斥反应仍比异种移植物快。尽管有研究表明非Gal抗体和αβ T细胞在异种移植物排斥反应中发挥作用,但对γδ T细胞参与异种移植物排斥反应的研究还很有限:方法:将野生型猪(n = 3)或GGTA1基因敲除猪(n = 3)的猪血管异种移植给6只雄性猴。我们测量了异种移植前后血液中γδT细胞的比例和T细胞受体(TCR)汇集。移植猪血管浸润免疫细胞在实验结束时可视化:结果:异种移植α-Gal缺陷猪血管后,血液中的γδT细胞扩增并浸润到移植血管的血管内膜。移植前和移植后的γδTCR反应谱分析显示,移植后δ链的使用发生了转变,δ1、δ3或δ7链的多个克隆型扩大。结论:异种移植显著改变了γδ TCR 反应谱系,表明γδ T 细胞在持续的异种活性免疫反应中发挥作用。
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来源期刊
Xenotransplantation
Xenotransplantation 医学-医学:研究与实验
CiteScore
6.80
自引率
15.40%
发文量
58
审稿时长
>12 weeks
期刊介绍: Xenotransplantation provides its readership with rapid communication of new findings in the field of organ and tissue transplantation across species barriers.The journal is not only of interest to those whose primary area is xenotransplantation, but also to veterinarians, microbiologists and geneticists. It also investigates and reports on the controversial theological, ethical, legal and psychological implications of xenotransplantation.
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