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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-06-1797.
Submitted June 5, 2003
Accepted September 4, 2003
Identification of the earliest prethymic T-cell progenitors in murine fetal blood
Tomokatsu Ikawa, Kyoko Masuda, Min Lu, Nagahiro Minato, Yoshimoto Katsura, and Hiroshi Kawamoto*
Department of Immunology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan; Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan
Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
Division of Cell Regeneration and Transplantation, Advanced Medical Research Center, Nihon University School of Medicine, Tokyo, Japan
* Corresponding author; email: kawamoto{at}imm.med.kyoto-u.ac.jp.
During murine fetal development, hematopoietic progenitors start to colonize the thymic anlage at day 11 of gestation via blood stream. The present study aims at identifying the earliest prethymic progenitors in circulation. Here, we show that the IL-7R+ cells in Lin - c-kit+ population are circulating exclusively between days 11 to 14 of fetal age. Clonal analysis revealed that these IL-7R+ cells mostly contain T cell lineage restricted progenitors (p-T). The proportion of circulating p-T reaches 30% of the total p-T during these fetal ages, whereas virtually all B cell lineage restricted progenitors stay in the fetal liver, suggesting that the p-T are selectively released to the circulation. The circulating p-T retain the potential to generate natural killer cells and dendritic cells and exhibit extensive proliferation before the occurrence of TCR chain gene rearrangement. We propose that the wave of p-T in fetal blood disclosed by this study represents the ontogenically earliest thymic immigrants.
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