Faculty Research 1990 - 1999

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

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Antigens-CD8: an, Bone-Marrow: cy, CD4-Positive-T-Lymphocytes: cy, Female, Fetal-Blood: cy, Human, In-Vitro, Mice, Mice-Inbred-Strains, Mice-SCID, Organ-Culture, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocyte-Subsets: cy, Thymus-Gland: cy

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Proc Natl Acad Sci U S A 1993 Nov 15;90(22):10778-82




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., CD8low, 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.

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