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Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes.

Carlyle JR, Michie AM, Furlonger C, Nakano T, Lenardo MJ, Paige CJ, Zúñiga-Pflücker JC - J. Exp. Med. (1997)

Bottom Line: The identification and functional properties of such a progenitor population remain undefined.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

ABSTRACT
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.

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Identification of a novel NK1.1+/CD117+ (c-kit) fetal thymocyte population during thymic ontogeny. Two-parameter flow cytometric analysis of cell surface expression of NK1.1 versus CD117 on fetal  thymocytes from timed-pregnant C57BL/6 mice (days 13, 14, 15, 16 of  gestation), fetal liver cells (day 13 of gestation), and thymocytes from adult  mice (8 wk old). NK1.1 and CD117 are coexpressed predominantly early  in thymocyte differentiation.
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Figure 1: Identification of a novel NK1.1+/CD117+ (c-kit) fetal thymocyte population during thymic ontogeny. Two-parameter flow cytometric analysis of cell surface expression of NK1.1 versus CD117 on fetal thymocytes from timed-pregnant C57BL/6 mice (days 13, 14, 15, 16 of gestation), fetal liver cells (day 13 of gestation), and thymocytes from adult mice (8 wk old). NK1.1 and CD117 are coexpressed predominantly early in thymocyte differentiation.

Mentions: Analysis of mouse day-13–16 fetal thymocytes, showed a small percentage of NK1.1+ lymphocytes (4–6%) as early as day 13 of gestation (Fig. 1). We were surprised to detect NK1.1+ cells in the fetal thymus, because NK1.1+ thymocytes were previously reported to be absent early in thymic ontogeny (6, 13, 14); however, an earlier report by Koo et al. (22) showed evidence for NK1.1 expression on early fetal thymocytes. Perhaps, the fact that NK1.1+ cells represent ⩽2% of total day-15 fetal thymocytes may explain why some investigators failed to notice this subset during thymic ontogeny (6, 13, 14). We further analyzed fetal thymocytes for expression of the SCF receptor, c-kit (CD117), which is characteristic of hematopoietic precursors in the fetal liver, bone marrow, and thymus (1–3, 14, 23–27). CD117 is expressed on the majority of day 13/14 NK1.1+ thymocytes but on very few NK1.1+ thymocytes later in ontogeny or in the adult thymus (Fig. 1). Significant expression of NK1.1 was not detectable among CD117+ fetal liver (FL) cells (Fig. 1), suggesting that it may be induced during or after migration to the thymus.


Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes.

Carlyle JR, Michie AM, Furlonger C, Nakano T, Lenardo MJ, Paige CJ, Zúñiga-Pflücker JC - J. Exp. Med. (1997)

Identification of a novel NK1.1+/CD117+ (c-kit) fetal thymocyte population during thymic ontogeny. Two-parameter flow cytometric analysis of cell surface expression of NK1.1 versus CD117 on fetal  thymocytes from timed-pregnant C57BL/6 mice (days 13, 14, 15, 16 of  gestation), fetal liver cells (day 13 of gestation), and thymocytes from adult  mice (8 wk old). NK1.1 and CD117 are coexpressed predominantly early  in thymocyte differentiation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198984&req=5

Figure 1: Identification of a novel NK1.1+/CD117+ (c-kit) fetal thymocyte population during thymic ontogeny. Two-parameter flow cytometric analysis of cell surface expression of NK1.1 versus CD117 on fetal thymocytes from timed-pregnant C57BL/6 mice (days 13, 14, 15, 16 of gestation), fetal liver cells (day 13 of gestation), and thymocytes from adult mice (8 wk old). NK1.1 and CD117 are coexpressed predominantly early in thymocyte differentiation.
Mentions: Analysis of mouse day-13–16 fetal thymocytes, showed a small percentage of NK1.1+ lymphocytes (4–6%) as early as day 13 of gestation (Fig. 1). We were surprised to detect NK1.1+ cells in the fetal thymus, because NK1.1+ thymocytes were previously reported to be absent early in thymic ontogeny (6, 13, 14); however, an earlier report by Koo et al. (22) showed evidence for NK1.1 expression on early fetal thymocytes. Perhaps, the fact that NK1.1+ cells represent ⩽2% of total day-15 fetal thymocytes may explain why some investigators failed to notice this subset during thymic ontogeny (6, 13, 14). We further analyzed fetal thymocytes for expression of the SCF receptor, c-kit (CD117), which is characteristic of hematopoietic precursors in the fetal liver, bone marrow, and thymus (1–3, 14, 23–27). CD117 is expressed on the majority of day 13/14 NK1.1+ thymocytes but on very few NK1.1+ thymocytes later in ontogeny or in the adult thymus (Fig. 1). Significant expression of NK1.1 was not detectable among CD117+ fetal liver (FL) cells (Fig. 1), suggesting that it may be induced during or after migration to the thymus.

Bottom Line: The identification and functional properties of such a progenitor population remain undefined.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus