Identification of the earliest prethymic T - cell progenitors in murine fetal

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 Linc-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 TCRβ chain gene rearrangement. We propose that the wave of p-T in fetal blood disclosed by this study represents the ontogenically earliest thymic immigrants. Introduction T lymphocytes, like other blood cells, are known to be derived from hematopoietic stem cells. Definitive hematopoiesis, which includes T cell development, is initiated in the aorta-gonad-mesonephros (AGM) region at 10.0 days postcoitus (dpc), and the major site of hematopoiesis shifts to the fetal liver (FL) at 11 dpc and subsequently to the bone marrow (BM) around birth. Colonization of the thymus anlage by hematopoietic cells is known to start at 11 dpc, and the thymic progenitors are shown to be transported via the blood stream. It has been reported that the progenitors capable of producing cells of various lineages are circulating during 10 dpc to 12 dpc, and these circulating multipotent only. For personal use at PENN STATE UNIVERSITY on February 23, 2013. bloodjournal.hematologylibrary.org From