PRETHYMIC CD34(-CELLS ARE NOT COMMITTED TO THE T-CELL LINEAGE() PROGENITORS CAPABLE OF DEVELOPING INTO T)

Progenitor cells that seed the fetal thymus are derived from the fetal liver and the bone marrow. These cells migrate through the fetal bloo d to the thymus. In this work, we address which peripheral progenitor cells have the potential to become T cells and whether these progenito r cells are already committed to the T cell lineage. All CD34(+)CD38(- ) precursor cells, regardless of their origin, are able to develop int o T cells in a hybrid human/mouse fetal thymic organ culture. Previous ly, we found that the more differentiated CD34(+)CD38(+) progenitor ce lls from fetal liver cannot develop into T cells. In this work, we sho w that CD34(+)CD38(+) cells from fetal bone marrow and cord blood are capable of T cell development, In spite of the T cell-developing poten tial, we did not detect rearrangements of TCR-delta or TCR-beta loci i n any of the CD34(+) peripheral precursors. CD34(+) fetal bone marrow cell subpopulations express pre-TCR-alpha. However, we could not detec t expression of pT alpha or of recombination-activating gene 1 in CD34 (+) cord blood cells. Since cord blood CD34(+) cells should contain th e direct progenitors of the CD34(+) thymocytes, our data do not suppor t the notion that in humans commitment to the T cell lineage occurs be fore the cells migrate into the thymus.