Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment.

Early human T cell development: analysis of the human thymus at the time of initial entry of hematopoietic stem cells into the fetal thymic microenvironment.
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DOI:
10.1084/jem.181.4.1445
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发表时间:
1995-04-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Heinly CS
Heinly CS
中科院分区:
其他
文献类型:
--
作者:
Haynes BF;Heinly CS

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为了确定在人类T细胞发育的早期阶段发生的事件,我们研究了造血干细胞在胎儿胸腺基底定殖前(7周)、期间(8.2周)和出生后(9.5周)的胎儿组织。计算7周和8.2周胸腺的近似体积发现,在此期间胸腺体积增加了35倍,7周胸腺高度为160微米,体积为0.008 mm3, 8.2周胸腺高度为1044微米,体积为0.296 mm3。8.2周的人胸腺细胞为CD4+ CD8 α +和细胞质CD3 epsilon+ cCD3 δ + CD8 β -和CD3 ζ -。只有5%的8周胸腺细胞是T细胞受体(TCR)- β +,小于0.1%是TCR- γ +,没有与TCR- δ单克隆抗体反应。在妊娠的前16周,我们观察到CD2和CD8 β(出现在9.5周)、CD1a、b和c分子(CD1b,然后是CD1c,然后是CD1a)、TCR分子(TCR- β,然后是TCR-delta)、CD45RA和CD45RO亚型、CD28(10周)、CD3 zeta(12-13周)和CD6(12、75周)的发育调节表达。虽然CD2在胸腺淋巴生成开始时不表达,但第二种CD58配体CD48在8.2周时表达,这表明CD48在胸腺发育早期起作用。综上所述,这些数据定义了人类胸腺中发生的序列表型和形态学变化,这些变化与造血干细胞在胸腺中的定植相一致,并提供了对人类T细胞发育早期阶段所涉及的分子的深入了解。
To determine events that transpire during the earliest stages of human T cell development, we have studied fetal tissues before (7 wk), during (8.2 wk), and after (9.5 wk to birth) colonization of the fetal thymic rudiment with hematopoietic stem cells. Calculation of the approximate volumes of the 7- and 8.2-wk thymuses revealed a 35-fold increase in thymic volumes during this time, with 7-wk thymus height of 160 microM and volume of 0.008 mm3, and 8.2-wk thymus height of 1044 microM and volume of 0.296 mm3. Human thymocytes in the 8.2-wk thymus were CD4+ CD8 alpha+ and cytoplasmic CD3 epsilon+ cCD3 delta+ CD8 beta- and CD3 zetta-. Only 5% of 8-wk thymocytes were T cell receptor (TCR)-beta+, < 0.1% were TCR-gamma+, and none reacted with monoclonal antibodies against TCR-delta. During the first 16 wk of gestation, we observed developmentally regulated expression of CD2 and CD8 beta (appearing at 9.5 wk), CD1a,b, and c molecules (CD1b, then CD1c, then CD1a), TCR molecules (TCR-beta, then TCR-delta), CD45RA and CD45RO isoforms, CD28 (10 wk), CD3 zeta (12-13 wk), and CD6 (12,75 wk). Whereas CD2 was not expressed at the time of initiation of thymic lymphopoiesis, a second CD58 ligand, CD48, was expressed at 8.2 wk, suggesting a role for CD48 early in thymic development. Taken together, these data define sequential phenotypic and morphologic changes that occur in human thymus coincident with thymus colonization by hematopoietic stem cells and provide insight into the molecules that are involved in the earliest stages of human T cell development.
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