Commitment to natural killer cells requires the helix–loop–helix inhibitor Id2

T Ikawa, S Fujimoto, H Kawamoto… - Proceedings of the …, 2001 - National Acad Sciences
T Ikawa, S Fujimoto, H Kawamoto, Y Katsura, Y Yokota
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
We have previously described how T and natural killer (NK) lineage commitment proceeds
from common T/NK progenitors (pT/NK) in the murine fetal thymus (FT), with the use of a
clonal assay system capable of discriminating pT/NK from unipotent T or NK lineage-
committed progenitors (pT and p-NK, respectively). The molecular mechanisms controlling
the commitment processes, however, are yet to be defined. In this study, we investigated the
progenitor activity of FT cells from Id2−/− mice that exhibit defective NK cell development. In …
We have previously described how T and natural killer (NK) lineage commitment proceeds from common T/NK progenitors (p-T/NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T/NK from unipotent T or NK lineage-committed progenitors (p-T and p-NK, respectively). The molecular mechanisms controlling the commitment processes, however, are yet to be defined. In this study, we investigated the progenitor activity of FT cells from Id2−/− mice that exhibit defective NK cell development. In the Id2−/− FT, NK cells were greatly reduced, and a cell population that exclusively contains p-NK in the wild-type thymus was completely missing. Id2−/− FT progenitors were unable to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single progenitor analysis demonstrated that all Id2−/− fetal thymic progenitors are destined for the T cell lineage, whereas progenitors for T/NK, T, and NK cell lineages were found in the control. Interestingly, the total progenitor number was similar between Id2−/− and Id2+/+ embryos analyzed. Expression of Id2 was correlated with p-NK activity. Our results suggest that Id2 is indispensable in thymic NK cell development, where it most probably restricts bipotent T/NK progenitors to the NK cell lineage.
National Acad Sciences