CHARACTERIZATION OF GAMMA-DELTA-T-CELL CLONES ISOLATED FROM HUMAN FETAL LIVER AND THYMUS

CHARACTERIZATION OF GAMMA-DELTA-T-CELL CLONES ISOLATED FROM HUMAN FETAL LIVER AND THYMUS
复制标题

DOI:
10.1002/eji.1830200619
复制
发表时间:
1990-06-01
影响因子:
5.4
通讯作者:
BOTTOMLY, K
BOTTOMLY, K
中科院分区:
医学3区
文献类型:
--
作者:
CARDING, SR;MCNAMARA, JG;BOTTOMLY, K

文献摘要

被引文献

相似文献

携带γ/的T细胞的起源和发育δ的T细胞受体(TcR)已在小鼠中被广泛研究。相比之下,对人类γ的发育模式和多样性知之甚少。δ的T细胞谱系。为了研究人γ/的全部功能,δ +在T细胞个体发生期间,我们分离了γ/T细胞的克隆群体。δ +从14周胎儿胸腺和肝脏的T细胞,并表征其TcR的分子组成。应用原位杂交技术检测了胎肝和胸腺中表达TcR基因的细胞。随后从表达细胞表面γ/的组织和克隆中分离一组代表体内发现的发育中的T细胞群的克隆。δ的受体被鉴定。虽然肝源性γ/.δ + T细胞克隆L2和胸腺衍生的γ/.δ + T细胞克隆T6具有相似的细胞表面表型,即CD 3+、CD 7+、CD 45+和CD 8-,它们与抗CD 2和抗CD 4抗体的反应性不同。L2为CD 2高、CD 4-,T6为CD 2低、CD 4低。这两个克隆具有类似于成人T细胞的效应子功能,如通过响应于通过CD 3/TcR复合物的刺激的细胞因子的合成和分泌所证明的。胎儿克隆的TcR组成的分析显示两个克隆具有相似或相同的γ。链组分C γ 1、J γ 1/2、V γ 8,并且两者都利用V δ。除V δ 1以外的基因片段。这种TcR基因型以前在成人γ/的分析中没有报道过。δ + T细胞。我们的研究已经鉴定了一个独特的人γ/。δ + T细胞可能来源于胸腺外,在胎儿期优先表达,可能是短暂表达。
The origin and development of T cells bearing .gamma./.delta. T cells receptors (TcR) has been extensively studied in the mouse. By contrast, little is known about development patterns and diversity of the humans .gamma./.delta. T cell lineage. To study the repertoire of human .gamma./.delta.+ T cells during T cell ontogeny, we have isolated clonal populations of .gamma./.delta.+ T cells from 14-week fetal thymus and liver and characterized the molecular composition of their TcR. The technique of in situ hybridization was used to identify cells expressing TcR genes in fetal liver and thymus. A panel of clones representative of developing T cell populations found in vivo was subsequently isolated from both tissues and clones expressing cell surface .gamma./.delta. receptors were identified. Although both the liver-derived .gamma./.delta.+ T cell clone, L2, and the thymus-derived .gamma./.delta.+ T cell clone, T6, had similar cell surface phenotypes, namely CD3+, CD7+, CD45+ and CD8-, their reactivity with anti-CD2 and -CD4 antibodies was different. L2 was CD2high, CD4- whereas T6 was CD2low, CD4low. Both clones possessed effector functions similar to those of adult T cells as demonstrated by the synthesis and secretion of cytokines in response to stimulation through the CD3/TcR complex. Analysis of the TcR composition of the fetal clones showed both clones to possess similar or identical .gamma. chain components, C.gamma.1, J.gamma.1/2, V.gamma.8, and both utilize V.delta. gene segments other than V.delta.1. This TcR genotype has not been previously reported in the analysis of adult .gamma./.delta.+ T cells. Our studies have identified a unique population of human .gamma./.delta.+ T cells that may be derived extrathymically and appear to be preferentially and perhaps transiently expressed during fetal life.