J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/173/10 $2.00
Volume 186, Number 2, July 21, 1997 173-182

Identification of a Novel Developmental Stage Marking Lineage Commitment of Progenitor Thymocytes

By James R. Carlyle,^* Alison M. Michie,^* Caren Furlonger, Toru Nakano,^§ Michael J. Lenardo, Christopher J. Paige,^* and Juan Carlos Zúñiga-Pflücker^*

From the ^* Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada;  The Wellesley Hospital Research Institute, Toronto, Ontario M4Y 1J3, Canada; ^§ Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Yamada-Oka 3-1, Suita, Osaka 565, Japan; and the  Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

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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