International Immunology, Vol. 13, No. 1, 105-117,
January 2001
© 2001 Japanese Society for Immunology
Progression of T cell lineage restriction in the earliest subpopulation of murine adult thymus visualized by the expression of lck proximal promoter activity
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
Correspondence to: T. Nakayama, Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
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 
ß and 
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.
Keywords: green fluorescence protein, T cell lineage commitment, transgenic
Transmitting editor: A. Singer
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Gatzka, R. H. Newton, and C. M. Walsh Altered Thymic Selection and Increased Autoimmunity Caused by Ectopic Expression of DRAK2 during T Cell Development J. Immunol., July 1, 2009; 183(1): 285 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-W. Chu, S. Schmitz, B. Choudhury, W. Telford, V. Kapoor, S. Garfield, D. Howe, and R. E. Gress Exogenous insulin-like growth factor 1 enhances thymopoiesis predominantly through thymic epithelial cell expansion Blood, October 1, 2008; 112(7): 2836 - 2846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Carl Jr., J.-Q. Liu, P. S. Joshi, H. Y. El-Omrani, L. Yin, X. Zheng, C. C. Whitacre, Y. Liu, and X.-F. Bai Autoreactive T Cells Escape Clonal Deletion in the Thymus by a CD24-Dependent Pathway J. Immunol., July 1, 2008; 181(1): 320 - 328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Akins and P. Dubey Noninvasive Imaging of Cell-Mediated Therapy for Treatment of Cancer J. Nucl. Med., June 1, 2008; 49(Suppl_2): 180S - 195S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Masuda, K. Kakugawa, T. Nakayama, N. Minato, Y. Katsura, and H. Kawamoto T Cell Lineage Determination Precedes the Initiation of TCRbeta Gene Rearrangement J. Immunol., September 15, 2007; 179(6): 3699 - 3706. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Manning, J. G.M. Ullman, J. M. Leatherman, J. M. Asquith, T. R. Hansen, T. D. Armstrong, D. J. Hicklin, E. M. Jaffee, and L. A. Emens A Vascular Endothelial Growth Factor Receptor-2 Inhibitor Enhances Antitumor Immunity through an Immune-Based Mechanism Clin. Cancer Res., July 1, 2007; 13(13): 3951 - 3959. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Rowbotham, A. L. Hager-Theodorides, M. Cebecauer, D. K. Shah, E. Drakopoulou, J. Dyson, S. V. Outram, and T. Crompton Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR repertoire selection in the thymus and peripheral T-cell activation Blood, May 1, 2007; 109(9): 3757 - 3766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Bartholdy, C. Du Roure, A. Bordon, D. Emslie, L. M. Corcoran, and P. Matthias The Ets factor Spi-B is a direct critical target of the coactivator OBF-1 PNAS, August 1, 2006; 103(31): 11665 - 11670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. O. Cowley, G. W. Muse, and T. Van Dyke A Dominant Interfering Bub1 Mutant Is Insufficient To Induce or Alter Thymic Tumorigenesis In Vivo, Even in a Sensitized Genetic Background Mol. Cell. Biol., September 1, 2005; 25(17): 7796 - 7802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Terra, I. Louis, R. Le Blanc, S. Ouellet, J. C. Zuniga-Pflucker, and C. Perreault T-cell generation by lymph node resident progenitor cells Blood, July 1, 2005; 106(1): 193 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. O. Manilay, A. C. Anderson, C. Kang, and E. A. Robey Impairment of Thymocyte Development by Dominant-Negative Kuzbanian (ADAM-10) Is Rescued by the Notch Ligand, Delta-1 J. Immunol., June 1, 2005; 174(11): 6732 - 6741. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Yucel, C. Kosan, F. Heyd, and T. Moroy Gfi1:Green Fluorescent Protein Knock-in Mutant Reveals Differential Expression and Autoregulation of the Growth Factor Independence 1 (Gfi1) Gene during Lymphocyte Development J. Biol. Chem., September 24, 2004; 279(39): 40906 - 40917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. El Kassar, P. J. Lucas, D. B. Klug, M. Zamisch, M. Merchant, C. V. Bare, B. Choudhury, S. O. Sharrow, E. Richie, C. L. Mackall, et al. A dose effect of IL-7 on thymocyte development Blood, September 1, 2004; 104(5): 1419 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Okada, C. Bakal, A. Shahinian, A. Elia, A. Wakeham, W.-K. Suh, G. S. Duncan, M. Ciofani, R. Rottapel, J. C. Zuniga-Pflucker, et al. Survivin Loss in Thymocytes Triggers p53-mediated Growth Arrest and p53-independent Cell Death J. Exp. Med., February 2, 2004; 199(3): 399 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. C. Gebuhr, G. I. Kovalev, S. Bultman, V. Godfrey, L. Su, and T. Magnuson The Role of Brg1, a Catalytic Subunit of Mammalian Chromatin-remodeling Complexes, in T Cell Development J. Exp. Med., December 15, 2003; 198(12): 1937 - 1949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Q. Shen, M. Lu, T. Ikawa, K. Masuda, K. Ohmura, N. Minato, Y. Katsura, and H. Kawamoto T/NK Bipotent Progenitors in the Thymus Retain the Potential to Generate Dendritic Cells J. Immunol., October 1, 2003; 171(7): 3401 - 3406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Garcia-Peydro, V. G. de Yebenes, and M. L. Toribio Sustained Notch1 signaling instructs the earliest human intrathymic precursors to adopt a {gamma}{delta} T-cell fate in fetal thymus organ culture Blood, October 1, 2003; 102(7): 2444 - 2451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Hahm, N. Arbour, D. Naniche, D. Homann, M. Manchester, and M. B. A. Oldstone Measles Virus Infects and Suppresses Proliferation of T Lymphocytes from Transgenic Mice Bearing Human Signaling Lymphocytic Activation Molecule J. Virol., March 15, 2003; 77(6): 3505 - 3515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ceredig The ontogeny of B cells in the thymus of normal, CD3{varepsilon} knockout (KO), RAG-2 KO and IL-7 transgenic mice Int. Immunol., January 1, 2002; 14(1): 87 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. W. Christopherson II, J. J. Campbell, and R. A. Hromas Transgenic overexpression of the CC chemokine CCL21 disrupts T-cell migration Blood, December 15, 2001; 98(13): 3562 - 3568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Taneda, S. Segerer, K. L. Hudkins, Y. Cui, M. Wen, M. Segerer, M. H. Wener, C. G. Khairallah, A. G. Farr, and C. E. Alpers Cryoglobulinemic Glomerulonephritis in Thymic Stromal Lymphopoietin Transgenic Mice Am. J. Pathol., December 1, 2001; 159(6): 2355 - 2369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Reizis and P. Leder The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor {alpha} Gene in Immature T Lymphocytes J. Exp. Med., October 1, 2001; 194(7): 979 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kikuchi, Y. Kawasaki, N. Ishii, Y. Sasaki, H. Asao, T. Takeshita, I. Miyoshi, N. Kasai, and K. Sugamura Suppression of thymic development by the dominant-negative form of Gads Int. Immunol., June 1, 2001; 13(6): 777 - 783. [Abstract] [Full Text] [PDF]
|
|