人体心脏瓣膜的免疫屏蔽

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2024-11-01 DOI:10.1016/j.jacbts.2024.07.003

Marijn C. Peters PhD , Arnaud Zaldumbide PhD , Esmee J. Groeneveld BSc , Martijn J.W.E. Rabelink BSc , Janneke H. Peerlings MSc , Antoon van den Bogaerdt MSc , Carlijn V.C. Bouten PhD , Rob C. Hoeben PhD , Marie-Jose Goumans PhD , Abraham van Wijk MD, PhD

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引用次数: 0

摘要

先天性心脏瓣膜有缺陷的儿童一生中需要多次供体瓣膜置换，因为这些瓣膜无法生长，并可能因免疫变性而导致早期衰竭。这项研究测试了慢病毒递送病毒免疫逃避基因 US2 和人类血清素 9 以保护人类心脏瓣膜免受免疫排斥。结果表明，我们可以有效下调心脏瓣膜细胞和完整心脏瓣膜组织中人类白细胞抗原的表达，从而降低人类白细胞抗原反应性 CD8+ T 细胞克隆的活性，而不会诱导细胞毒性。这项研究证明了人类心脏瓣膜的免疫屏蔽作用，使我们更接近于为儿科患者提供持久的瓣膜移植。

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Immune Shielding of Human Heart Valves

Children born with defective heart valves require multiple donor valve replacements throughout life, because these cannot grow and can cause early failure through immune degeneration. This study tests the lentiviral delivery of viral immune evasion genes US2 and human serpin 9 to shield human heart valves from immune rejection. The results show we can efficiently down-regulate human leukocyte antigen expression in heart valve cells and in intact heart valve tissue resulting in decreased activity of a human leukocyte antigen–reactive CD8+ T-cell clone without inducing cytotoxicity. This study demonstrates immune shielding of human heart valves and brings us closer to a durable valve graft in pediatric patients.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.