Identification of pro-thymocytes in murine fetal blood: T lineage commitment can precede thymus colonization

Phenotype and commitment of thymus-colonizing precursors are unknown. Here we report the identification of T lineage-committed precursors (designated prothymocytes) in murine fetal blood at day 15.5 of development. Fetal blood pro-thymocytes are Thy-1+c-kit(low)CD3- in contrast to fetal blood-derived pluripotent hematopoietic progenitors which are Thy-1-c-kit+. Upon transfer into the thymus, fetal blood pro-thymocytes generate a single wave of CD4+CD8+ thymocytes and subsequently mature TCR alpha beta+ peripheral T cells. However, fetal blood pro-thymocytes lack multipotent progenitor potential since they fail to reconstitute B lymphocytes and myeloid and erythroid lineages. In contrast, T and B lymphocytes as well as myeloid and erythroid lineages are reconstituted from fetal blood-derived pluripotent progenitors. Pro-thymocytes are equally present in peripheral blood of athymic fetal mice, suggesting that this novel precursor population is T lineage-committed prior to thymus colonization and represents the earliest T lineage precursor identified.