Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity |
| |
Authors: | Shimizu C Kawamoto H Yamashita M Kimura M Kondou E Kaneko Y Okada S Tokuhisa T Yokoyama M Taniguchi M Katsura Y Nakayama T |
| |
Institution: | CREST (Core Research for Evolution Science and Technology) Project, Japan Science and Technology Corporation (JST), and Department of Molecular Immunology, and
1 Department of Developmental Genetics, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba 260-8670, Japan
2 Department of Immunology, Institute for Frontier Medical Science, Kyoto University, Kyoto 606-8507, Japan
3 Reproductive Engineering Section, Mitsubishi Kasei Institute of Life Sciences, Machida, Tokyo 194-8511, Japan |
| |
Abstract: | The proximal promoter of lck directs gene expression exclusivelyin T cells. To investigate the developmental regulation of thelck proximal promoter activity and its relationship to T celllineage commitment, a green fluorescence protein (GFP) transgenic(Tg) mouse in which the GFP expression is under the controlof the proximal promoter of lck was created. In the adult GFP-Tgmice, >90% of CD4+CD8+ and CD4+CD8 thymocytes, andthe majority of CD4CD8+ and CD4CD8 double-negative(DN)] thymocytes were highly positive for GFP. Slightly lowerbut substantial levels of expression of GFP was also observedin mature splenic T cells. No GFP+ cells was detected in non-Tlineage subsets, including mature and immature B cells, CD5+B cells, and NK cells, indicating a preserved tissue specificityof the promoter. The earliest GFP+ cells detected were foundin the CD44+CD25 DN thymocyte subpopulation. The developmentalpotential of GFP and GFP+ cells in the CD44+CD25DN fraction was examined using in vitro culture systems. Thegeneration of substantial numbers of ß and ![{gamma}](http://intimm.oxfordjournals.org/math/gamma.gif) T cells aswell as NK cells was demonstrated from both GFP and GFP+cells. However, no development of B cells or dendritic cellswas detected from GFP+ CD44+CD25 DN thymocytes. Theseresults suggest that the progenitors expressing lck proximalpromoter activity in the CD44+CD25 DN thymocyte subsethave lost most of the progenitor potential for the B and dendriticcell lineage. Thus, progression of T cell lineage restrictionin the earliest thymic population can be visualized by lck proximalpromoter activity, suggesting a potential role of Lck in theT cell lineage commitment. |
| |
Keywords: | green fluorescence protein T cell lineage commitment transgenic |
本文献已被 PubMed Oxford 等数据库收录! |
|