Commitment to natural killer cells requires the helix-loop-helix inhibitor ld2

Tomokatsu Ikawa, Shinji Fujimoto, Hiroshi Kawamoto, Yoshimoto Katsura, Yoshifumi Yokota

Research output: Contribution to journalArticlepeer-review

136 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5164-5169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number9
DOIs
Publication statusPublished - 24-04-2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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