Pathways from hematopoietic stem cells to thymocytes

A long-standing debate has been whether commitment to the T cell lineage occurs exclusively following thymus colonization, or whether prethymic T lineage restricted progenitors exist. Recently, the analysis of murine fetal blood for the presence of hematopoietic progenitor cells has led to the identification of a T lineage committed precursor population (designated prothymocytes). Fetal blood prothymocytes lack multipotent progenitor potential as shown by the fact that they fail to reconstitute B lymphocyte, myeloid anderythroid lineages. In addition to prothymocytes, fetal blood also contains a phenotypically distinct, pluripotent progenitor population which can reconstitute both T and B lymphocytes as well as myeloid and erythroid lineages. The identification of a circulating, T lineage restricted precursor population, which is also found in the blood of fetal athymic mice, provides strong evidence that T lineage commitment can precede thymus colonization. The thymus is not, however, exclusively colonized by prothymocytes. Under appropriate developmental conditions, multipotent precursor activity for non-T lineages such as B lymphocytes and thymic dendritic cells can be revealed within the intrathymic precursor pool. Moreover, evidence has been accumulated for a common progenitor for T cells and natural killer cells whch may be distinct from multipotent intrathymic progenitors.