Putative prethymic T cell precursors within the early human embryonic liver: a molecular and functional analysis.
Putative prethymic T cell precursors within the early human embryonic liver: a molecular and functional analysis.
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DOI：
10.1084/jem.177.1.19
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发表时间：
1993-01-01
期刊：
影响因子：
--
通讯作者：
Toribio ML
中科院分区：
文献类型：
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作者：
Sánchez MJ;Gutiérrez-Ramos JC;Fernández E;Leonardo E;Lozano J;Martínez C;Toribio ML
利用一组广泛的单抗进行表型分析，对早期人类胎儿肝脏中存在的造血细胞进行了特征分析。在获得T细胞、B细胞或髓系特异性表面标记物之前以及胸腺内定植时间之前，所有胎肝造血细胞均表达极晚期抗原4和白细胞功能相关抗原3细胞黏附受体和4F2细胞激活分子。分子研究表明，白介素2受体β(IL-2Rβ)在个体发育早期的胚胎肝脏中也有表达。相反，IL-2Rα或IL-2转录本在胎肝细胞中未见表达，而IL-4基因在一小部分胎肝细胞亚群中有转录。通过编码CD3-T细胞受体(TCR)复合体的Gamma、Delta、epsilon和Zeta不变链的基因的表达，在造血性胎肝细胞中鉴定出可能的T细胞前体。然而，没有检测到多态的α和βTCR基因的转录。体外功能分析进一步证明，这些早期胚胎的胎肝造血细胞能够在包括IL-4和IL-2在内的T细胞生长因子的作用下增殖。然而，尽管IL-4诱导的增殖与表达CD14髓系抗原的CD45+CD7-CD4迟钝细胞以及CD34+原始造血祖细胞的出现相似，但IL-2诱导的T细胞分化为CD45+CD7+CD8+CD3-未成熟T细胞。此外，与胸腺上皮细胞单层共培养提供了额外的证据，表明早期胎肝造血细胞可能含有非常原始的T细胞前体，这些T细胞前体能够在体外分化为TCRα/β+成熟T细胞。因此，我们的结果表明，在原始胎肝造血祖细胞触发T细胞特异性成熟程序后，胸腺内由上皮细胞提供的特定信号可能满足驱动胸腺前承诺T细胞前体终末分化的要求。
Hematopoietic cells present in the liver in early human fetal life were characterized by phenotypic analysis using a broad panel of monoclonal antibodies. Expression of very late antigen 4 and leukocyte function- associated antigen 3 cell adhesion receptors and 4F2 cell activation molecules was found in all fetal liver hematopoietic cells before acquisition of T cell-, B cell-, or myeloid-specific surface markers, and before the time of intrathymic colonization. Molecular studies showed that expression of the interleukin 2 receptor beta (IL-2R beta) also occurred in the embryonic liver at this early ontogenic stage. In contrast, no expression of IL-2R alpha or IL-2 transcripts was found in fetal liver cells, whereas transcription of the IL-4 gene was detected in a small fetal liver cell subset. Putative T cell precursors were identified among the hematopoietic fetal liver cells by the expression of genes encoding the gamma, delta, epsilon, and zeta invariant chains of the CD3-T cell receptor (TCR) complex. However, no transcription of the polymorphic alpha and beta TCR genes was detected. Functional in vitro assays further demonstrated that fetal liver hematopoietic cells from those early embryos were capable of proliferating in response to T cell growth factors, including IL-4 and IL-2. However, whereas IL-4- induced proliferation paralleled the appearance in vitro of CD45+CD7- CD4dull cells expressing the CD14 myeloid antigen, as well as of CD34+ primitive hematopoietic progenitors, differentiation into CD45+CD7+CD8+CD3- immature T cells was observed when using IL-2. Moreover, coculture with thymic epithelial cell monolayers provided additional evidence that early fetal liver hematopoietic cells may include very primitive T cell precursors, which were able to differentiate in vitro into TCR alpha/beta+ mature T cells. Therefore, our results indicate that, after triggering of the T cell-specific maturation program in primitive fetal liver hematopoietic progenitors, specific signals provided intrathymically by epithelial cells may fulfill the requirements to drive terminal differentiation of prethymically committed T cell precursors.