Article
- The EMBO Journal (2005) 24, 4052 - 4060
- doi:10.1038/sj.emboj.7600878
Published online: 17 November 2005
Subject Categories:
Prethymic T-cell development defined by the expression of paired immunoglobulin-like receptors
Kyoko Masuda1,2, Hiromi Kubagawa3, Tomokatsu Ikawa4, Ching-Cheng Chen3, Kiyokazu Kakugawa2, Masakazu Hattori1, Ryoichiro Kageyama5, Max D Cooper3, Nagahiro Minato1, Yoshimoto Katsura6 and Hiroshi Kawamoto2
- Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
- Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
- Department of Pathology, Division of Developmental and Clinical Immunology, University of Alabama, Birmingham, AL, USA
- Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
- Laboratory of Growth Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan
- Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan
Correspondence to:
Hiroshi Kawamoto, Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama 230-0045, Japan. Tel.: +81 45 503 7010; Fax: +81 45 503 7009; E-mail: kawamoto@rcai.riken.jp
Received 6 July 2005; Accepted 25 October 2005
Abstract
T cells are produced in the thymus from progenitors of extrathymic origin. As no specific markers are available, the developmental pathway of progenitors preceding thymic colonization remains unclear. Here we show that progenitors in murine fetal liver and blood, which are capable of giving rise to T cells, NK cells and dendritic cells, but not B cells, can be isolated by their surface expression of paired immunoglobulin-like receptors (PIR). PIR expression is maintained until the earliest intrathymic stage, then downregulated before the onset of CD25 expression. Unlike intrathymic progenitors, generation of prethymic PIR+ progenitors does not require Hes1-mediated Notch signaling. These findings disclose a prethymic stage of T-cell development programmed for immigration of the thymus, which is genetically separable from intrathymic stages.
Keywords:
- clonal analysis,
- fetal liver,
- lineage commitment,
- T-cell development,
- thymus
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