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.