Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles (ULB), Brussels, Belgium.
Institute for Medical Immunology, Université Libre de Bruxelles (ULB), Gosselies, Belgium.
Immunol Rev. 2023 May;315(1):89-107. doi: 10.1111/imr.13184. Epub 2023 Jan 10.
While γδ T cells are present virtually in all vertebrates, there is a remarkable lack of conservation of the TRG and TRD loci underlying the generation of the γδ T cell receptor (TCR), which is associated with the generation of species-specific γδ T cells. A prominent example is the human phosphoantigen-reactive Vγ9Vδ2 T cell subset that is absent in mice. Murine γδ thymocyte cells were among the first immune cells identified to follow a wave-based layered development during embryonic and early life, and since this initial observation, in-depth insight has been obtained in their thymic ontogeny. By contrast, less is known about the development of human γδ T cells, especially regarding the generation of γδ thymocyte waves. Here, after providing an overview of thymic γδ wave generation in several vertebrate classes, we review the evidence for γδ waves in the human fetal thymus, where single-cell technologies have allowed the breakdown of human γδ thymocytes into functional waves with important TCR associations. Finally, we discuss the possible mechanisms contributing to the generation of waves of γδ thymocytes and their possible significance in the periphery.
虽然 γδ T 细胞几乎存在于所有脊椎动物中，但生成 γδ T 细胞受体（TCR）所必需的 TRG 和 TRD 基因座的保守性极差，这与产生物种特异性 γδ T 细胞有关。一个突出的例子是人类磷酸抗原反应性 Vγ9Vδ2 T 细胞亚群，而在小鼠中则不存在。鼠 γδ 胸腺细胞是最早被鉴定出在胚胎期和生命早期遵循波状分层发育的免疫细胞之一，自最初的观察以来，人们对其胸腺发生有了深入的了解。相比之下，关于人类 γδ T 细胞的发育，特别是关于 γδ 胸腺细胞波的产生，人们知之甚少。在这里，在概述了几个脊椎动物类群的胸腺 γδ 波产生之后，我们回顾了人类胎儿胸腺中 γδ 波的证据，单细胞技术允许将人类 γδ 胸腺细胞分解为具有重要 TCR 关联的功能性波。最后，我们讨论了可能有助于产生 γδ 胸腺细胞波的机制及其在外周组织中的可能意义。
