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

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 interleukin-7 receptor-positive (IL-7R⁺) cells in Lin^- c-kit⁺ population are circulating exclusively between days 11 and 14 of fetal age. Clonal analysis revealed that these IL-7R⁺ cells mostly contain T-cell lineage-restricted progenitors (p-Ts). The proportion of circulating p-Ts reaches 30% of the total p-Ts during these fetal ages, whereas virtually all B-cell lineage-restricted progenitors stay in the fetal liver, suggesting that the p-Ts are selectively released to the circulation. The circulating p-Ts retain the potential to generate natural killer cells and dendritic cells and exhibit extensive proliferation before the occurrence of T-cell receptor β (TCRβ) chain gene rearrangement. We propose that the wave of p-Ts in fetal blood disclosed by this study represents the ontogenically earliest thymic immigrants.