International Immunology Advance Access originally published online on August 14, 2007
International Immunology 2007 19(10):1175-1182; doi:10.1093/intimm/dxm085
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Forced expression of Id2 in fetal thymic T cell progenitors allows some of their progeny to adopt NK cell fate
1 Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan
2 Department of Biochemistry, School of Medicine, Fukui University, Fukui 910-1193, Japan
3 Present address: Laboratory for Lymphocyte Development, Riken Research Center for Allergy and Immunology, Yokohama 230-0045, Japan
Correspondence to: S. Fujimoto; E-mail: fujimoto{at}frontier.kyoto-u.ac.jp
The E proteins are indispensable for early T cell development. On the other hand, we previously demonstrated that their inhibitor Id2 is essential for NK lineage commitment from bipotent progenitors generating both T and NK cells (p-T/NK). To shed more light on the role of E proteins and Id2 in the development of early intrathymic progenitors, we performed a clonal analysis: individual fetal thymic CD4–CD8–CD44+CD25–CD122– (DN1CD122–) cells were retrovirally transduced with an Id2-internal ribosomal entry site (IRES)-green fluorescent protein (GFP) (Id2-GFP) gene or a control IRES-GFP (GFP) gene, and cultured in a modified fetal thymus organ culture able to support T and NK cell development. After the culture, both T and NK cells, T cells and no NK cells, NK cells and no T cells, or completely no cells were generated from single cells in each lobe. Hence, the seeded cells were regarded as p-T/NK, unipotent progenitors generating T cells (p-T), unipotent NK progenitors, or cells without progenitor activity, respectively. With Id2-GFP transduction, p-T disappeared and more p-T/NK emerged than with GFP transduction. This increase corresponded to the number of p-T that was counted when the vector-transduced-DN1CD122– cells of the same number were examined. Additionally, a fraction of GFP– NK cells obtained after Id2-GFP transduction underwent TCRß D–J rearrangement. Our data strongly suggest that forced expression of Id2 allows some progeny of p-T to adopt an NK cell fate, and that p-T retain a program for NK lineage development that can be implemented by inhibiting the function of E proteins.
Keywords: cell fate change, clonal assay, E proteins, Id2, NK lineage commitment, retrovirus vector, T lineage commitment
Transmitting editor: T. Saito
Received 27 November 2006, accepted 3 July 2007.