HUMAN BONE-MARROW AND UMBILICAL-CORD BLOOD-CELLS GENERATE CD4-POSITIVE T-CELLS IN MURINE FETAL THYMUS ORGAN-CULTURE( AND CD8+ SINGLE)

Murine fetal thymus lobes isolated from both normal and scid/scid mice can be colonized by donor cells from either human bone marrow or huma n umbilical cord blood in vitro. Subsequent organ culture results in a transient production of a few CD4+ CD8+ (double-positive) cells and t hen the accumulation of CD4+ or CD8+ (single-positive) T cells. A sign ificant number of immature T-cell intermediates (e.g., CD8low, CD3-/lo w cells) were present in early organ cultures, suggesting that these w ere progenitors of the mature CD3+/high single-positive T cells that d ominated late cultures. Depletion of mature T cells from the donor-cel l populations did not affect their ability to colonize thymus lobes. H owever, colonization depended on the presence of CD7+ progenitor T cel ls. Limiting dilution experiments using mature T-cell populations (hum an peripheral blood leukocytes, human bone marrow cells, and human umb ilical cord blood cells) suggested that thymic organ culture supports the growth of progenitor T cells but does not support the growth of ma ture human T cells. Each of these donor populations produced single-po sitive populations with different CD4/CD8 ratios, suggesting that prec ursor cells from different sources differ qualitatively in their capac ity to differentiate into T cells.