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., 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.
Yeoman
H
H
Department of Microbiology and Immunology, University of Arizona, Tucson 85721.
Gress
R E
RE
Bare
C V
CV
Leary
A G
AG
Boyse
E A
EA
Bard
J
J
Shultz
L D
LD
Harris
D T
DT
DeLuca
D
D
D000818:Animals; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D009924:Organ Culture Techniques; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D016827:CD8 Antigens