Human Bone Marrow and Umbilical Cord Blood Cells Generate CD4+and CD8+Single-Positive T Cells in Murine Fetal Thymus Organ Culture

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 90; no. 22; pp. 10778 - 10782
• Main Authors: Yeoman, Helen, Gress, Ronald E., Bare, Catherine V., Leary, Anne G., Boyse, Edward A., Bard, Judith, Shultz, Leonard D., Harris, David T., DeLuca, Dominick
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.11.1993; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Biochemistry; Biological and medical sciences; Blood cells; Bone marrow; Bone Marrow Cells; CD4-Positive T-Lymphocytes - cytology; CD8 Antigens - analysis; Cultured cells; Developmental biology; Female; Fetal Blood - cytology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunity (Disease); Immunobiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Medical research; Mice; Mice, Inbred Strains; Mice, SCID; Organ Culture Techniques; Progenitor cells; T cell antigen receptors; T lymphocytes; T lymphoid precursor cells; T-Lymphocyte Subsets - cytology; Thymocytes; Thymus Gland - cytology; Transplants & implants; Human; Thymus gland; Rodentia; Organotypic culture; Cell differentiation; Precursor; Blood; Vertebrata; Mammalia; Mouse; Hematopoiesis; T-Lymphocyte; Bone marrow; Fetus; Umbilical cord
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.22.10778

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-/lowcells) were present in early organ cultures, suggesting that these were progenitors of the mature CD3+/highsingle-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.