Identification of a novel developmental stage marking lineage commitment of progenitor thymocytes.
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.
Carlyle
J R
JR
Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Michie
A M
AM
Furlonger
C
C
Nakano
T
T
Lenardo
M J
MJ
Paige
C J
CJ
Zúñiga-Pflücker
J C
JC
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D005333:Fetus / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D007694:Killer Cells, Natural / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*
D019009:Proto-Oncogene Proteins c-kit