Human bone marrow and umbilical cord blood cells generate CD4⁺ and CD8⁺ single-positive T cells in murine fetal thymus organ culture

Murine fetal thymus lobes isolated from both normal and scid/scid mice can be colonized by donor cells from either human bone marrow or human umbilical cord blood in vitro. Subsequent organ culture results in a transient production of a few CD4⁺ CD8⁺ (double-positive) cells and then the accumulation of CD4⁺ or CD8⁺ (single-positive) T cells. A significant number of immature T-cell intermediates (e.g., CD8^low, CD3^-/low cells) were present in early organ cultures, suggesting that these were progenitors of the mature CD3^+/high single-positive T cells that dominated late cultures. Depletion of mature T cells from the donor-cell populations did not affect their ability to colonize thymus lobes. However, colonization depended on the presence of CD7⁺ progenitor T cells. Limiting dilution experiments using mature T-cell populations (human peripheral blood leukocytes, human bone marrow cells, and human umbilical cord blood cells) suggested that thymic organ culture supports the growth of progenitor T cells but does not support the growth of mature human T cells. Each of these donor populations produced single-positive populations with different CD4/CD8 ratios, suggesting that precursor cells from different sources differ qualitatively in their capacity to differentiate into T cells.