The proximal promoter of lck directs gene expression exclusively in T cells. To investigate the developmental regulation of the lck proximal promoter activity and its relationship to T cell lineage commitment, a green fluorescence protein (GFP) transgenic (Tg) mouse in which the GFP expression is under the control of the proximal promoter of lck was created. In the adult GFP-Tg mice, >90% of CD4+CD8+ and CD4+CD8- thymocytes, and the majority of CD4-CD8+ and CD4- CD8- [double-negative (DN)] thymocytes were highly positive for GFP. Slightly lower but substantial levels of expression of GFP was also observed in mature splenic T cells. No GFP+ cells was detected in non-T lineage subsets, including mature and immature B cells, CD5+ B cells, and NK cells, indicating a preserved tissue specificity of the promoter. The earliest GFP+ cells detected were found in the CD44+ CD25- DN thymocyte subpopulation. The developmental potential of GFP- and GFP+ cells in the CD44+CD25- DN fraction was examined using in vitro culture systems. The generation of substantial numbers of αβ and γδ T cells as well as NK cells was demonstrated from both GFP- and GFP+ cells. However, no development of B cells or dendritic cells was detected from GFP+ CD44+CD25- DN thymocytes. These results suggest that the progenitors expressing lck proximal promoter activity in the CD44+ CD25- DN thymocyte subset have lost most of the progenitor potential for the B and dendritic cell lineage. Thus, progression of T cell lineage restriction in the earliest thymic population can be visualized by lck proximal promoter activity, suggesting a potential role of Lck in the T cell lineage commitment.
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