Forced expression of Id2 in fetal thymic T cell progenitors allows some of their progeny to adopt NK cell fate.
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 TCRbeta 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.
Fujimoto
Shinji
S
Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. fujimoto@frontier.kyoto-u.ac.jp
Ikawa
Tomokatsu
T
Kina
Tatsuo
T
Yokota
Yoshifumi
Y
D000818:Animals; D019070:Cell Lineage; D005333:Fetus / Q000166:cytology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D051797:Inhibitor of Differentiation Protein 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D012190:Retroviridae; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D014161:Transduction, Genetic
C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D049452:Green Fluorescent Proteins