De Rosa Stephen C, Andrus James P, Perfetto Stephen P, Mantovani John J, Herzenberg Leonard A, Herzenberg Leonore A, Roederer Mario
Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2004 Feb 1;172(3):1637-45. doi: 10.4049/jimmunol.172.3.1637.
T cell receptors consist either of an alpha-chain combined with a beta-chain or a gamma-chain combined with a delta-chain. alphabeta T cells constitute the majority of T cells in human blood throughout life. Flow cytometric analyses presented in this study, which focus on the representation of the developmental (naive and memory) subsets of gammadelta T cells, show by function and phenotype that this lineage contains both naive and memory cells. In addition, we show that the representation of naive T cells is higher among alphabeta than gammadelta T cells in adults and that the low frequency of naive gammadelta T cells in adults reflects ontological differences between the two major gammadelta subsets, which are distinguished by expression of Vdelta1 vs Vdelta2 delta-chains. Vdelta1 cells, which mirror alphabeta cells with respect to naive representation, predominate during fetal and early life, but represent the minority of gammadelta cells in healthy adults. In contrast, Vdelta2 cells, which constitute the majority of adult gammadelta cells, show lower frequencies of naive cells than Vdelta1 early in life and show vanishingly small naive frequencies in adults. In essence, nearly all naive Vdelta2 cells disappear from blood by 1 year of life. Importantly, even in children less than 1 year old, most of the nonnaive Vdelta2 cells stain for perforin and produce IFN-gamma after short-term in vitro stimulation. This represents the earliest immunological maturation of any lymphocyte compartment in humans and most likely indicates the importance of these cells in controlling pathology due to common environmental challenges.
T细胞受体由与β链结合的α链或与δ链结合的γ链组成。αβ T细胞在人的一生中构成血液中T细胞的大多数。本研究中进行的流式细胞术分析聚焦于γδ T细胞发育（幼稚和记忆）亚群的表现，从功能和表型上表明该谱系同时包含幼稚细胞和记忆细胞。此外，我们表明，在成年人中，幼稚T细胞在αβ T细胞中的占比高于γδ T细胞，并且成年人中幼稚γδ T细胞的低频率反映了两个主要γδ亚群之间的本体差异，这两个亚群通过Vδ1与Vδ2 δ链的表达来区分。Vδ1细胞在幼稚细胞占比方面与αβ细胞相似，在胎儿期和生命早期占主导，但在健康成年人中仅占γδ细胞的少数。相比之下，构成成年γδ细胞大多数的Vδ2细胞，在生命早期幼稚细胞的频率低于Vδ1细胞，在成年人中幼稚细胞的频率极低。本质上，几乎所有幼稚Vδ2细胞在1岁时就从血液中消失。重要的是，即使在1岁以下的儿童中，大多数非幼稚Vδ2细胞也能被穿孔素染色，并在短期体外刺激后产生干扰素-γ。这代表了人类任何淋巴细胞区室最早的免疫成熟，很可能表明这些细胞在应对常见环境挑战所导致的病理过程中具有重要作用。
