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PMID: 11296270 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 98 ·No. 9 ·2001-04-24 ·Pages 5164-9

Ikawa T, Fujimoto S, Kawamoto H, Katsura Y, Yokota Y

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.

MeSH Terms
Animals Cell Differentiation/drug effects Cell Lineage/drug effects Cells, Cultured DNA-Binding Proteins/chemistry,genetics,metabolism Flow Cytometry Gene Deletion Helix-Loop-Helix Motifs Hyaluronan Receptors/metabolism Inhibitor of Differentiation Protein 2 Interleukin-2/pharmacology Killer Cells, Natural/cytology,drug effects,metabolism Lymphocyte Count Mice Mice, Inbred C57BL Mice, Knockout Models, Immunological Organ Culture Techniques RNA, Messenger/genetics,metabolism Receptors, Interleukin-2/analysis,metabolism Repressor Proteins Reverse Transcriptase Polymerase Chain Reaction Stem Cells/cytology,drug effects,metabolism Thymus Gland/cytology,drug effects,embryology,metabolism Transcription Factors
Chemicals
DNA-Binding Proteins Hyaluronan Receptors Idb2 protein, mouse Inhibitor of Differentiation Protein 2 Interleukin-2 RNA, Messenger Receptors, Interleukin-2 Repressor Proteins Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ikawa T
Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Shogoin Kawahara-cho 53, Sakyo-ku, 606-8507 Kyoto, Japan.
Fujimoto S
Kawamoto H
Katsura Y
Yokota Y
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.091537598
Published
2001-04-24
Epub
2001-00-10
Pages
5164-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC33181
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.091537598 PMC Full Text View journal details
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