Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes.
Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes.
复制标题
DOI：
10.1084/jem.186.2.173
复制
发表时间：
1997-07-21
期刊：
影响因子：
--
通讯作者：
Zúñiga-Pflücker JC
中科院分区：
文献类型：
--
作者：
Carlyle JR;Michie AM;Furlonger C;Nakano T;Lenardo MJ;Paige CJ;Zúñiga-Pflücker JC
T和自然杀伤(NK)淋巴细胞的双能祖细胞被认为存在于早期前体胸腺细胞中。这种祖细胞群体的鉴定和功能特性仍未确定。我们报告了在胎儿胸腺个体发育中发现的一个新的发育阶段，该阶段描述了一群T/NK承诺的祖细胞(NK1.1+/CD117+/CD44+/CD25−)。处于发育阶段的胸腺细胞在表型和功能上可与多能淋巴限制(B、T和NK)前体胸腺细胞池相区别。多能前体胸腺细胞或胎肝来源的造血祖细胞暴露于胸腺基质可诱导分化为双能发育阶段。持续暴露在胸腺微环境中会导致T细胞谱系的主要承诺，而与骨髓来源的基质细胞系共培养会产生成熟的NK细胞。因此，胸腺诱导分化是多能祖细胞阶段T和NK淋巴细胞命运的限制点。
Bipotent progenitors for T and natural killer (NK) lymphocytes are thought to exist among early precursor thymocytes. The identification and functional properties of such a progenitor population remain undefined. We report the identification of a novel developmental stage during fetal thymic ontogeny that delineates a population of T/NK-committed progenitors (NK1.1+/CD117+/CD44+/CD25−). Thymocytes at this stage in development are phenotypically and functionally distinguishable from the pool of multipotent lymphoid-restricted (B, T, and NK) precursor thymocytes. Exposure of multipotent precursor thymocytes or fetal liver– derived hematopoietic progenitors to thymic stroma induces differentiation to the bipotent developmental stage. Continued exposure to a thymic microenvironment results in predominant commitment to the T cell lineage, whereas coculture with a bone marrow–derived stromal cell line results in the generation of mature NK cells. Thus, the restriction point to T and NK lymphocyte destinies from a multipotent progenitor stage is marked by a thymus-induced differentiation step.