Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2.
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.
Ikawa
T
T
Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Shogoin Kawahara-cho 53, Sakyo-ku, 606-8507 Kyoto, Japan.
Fujimoto
S
S
Kawamoto
H
H
Katsura
Y
Y
Yokota
Y
Y
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D017353:Gene Deletion; D018257:Helix-Loop-Helix Motifs; D018960:Hyaluronan Receptors / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018448:Models, Immunological; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D018960:Hyaluronan Receptors; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D012097:Repressor Proteins; D014157:Transcription Factors