Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity

Chiori Shimizu, Hiroshi Kawamoto, Masakatsu Yamashita, Motoko Kimura, Eisuke Kondou, Yoshikatsu Kaneko, Seiji Okada, Takeshi Tokuhisa, Minesuke Yokoyama, Masaru Taniguchi, Yoshimoto Katsura, Toshinori Nakayama

Research output: Contribution to journalArticlepeer-review

70 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)105-117
Number of pages13
JournalInternational Immunology
Volume13
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity'. Together they form a unique fingerprint.

Cite this