T lymphocyte differentiation in vitro from adult human prethymic CD34+ bone marrow cells

doi:10.1084/jem.177.6.1531

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T lymphocyte differentiation in vitro from adult human prethymic CD34+ bone marrow cells

GE Tjonnfjord, OP Veiby, R Steen and T Egeland
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.

Pluripotent lymphohematopoietic stem cells are probably confined to bone marrow cells expressing CD34 surface molecules. To investigate the capacity of adult human CD34+ bone marrow cells to differentiate along the T lymphoid lineage, we plated purified CD34+ cells from healthy adults in liquid culture on adherent thymic stromal cells prepared from HLA- or blood group-mismatched postnatal thymic tissue. We show that purified CD34+CD3-CD4-CD8- bone marrow cells contained progenitors with the ability to differentiate into CD4+ and CD8+ T lymphocytes expressing surface (s)CD3 and T cell receptor alpha/beta in vitro. These progenitors were found in the CD34+CD2+sCD3-CD4-CD8-, CD34+CD7+sCD3-CD4-CD8-, and CD34+CD2+CD7+sCD3-CD4-CD8-, as well as in the CD34+CD2-sCD3-CD4-CD8-, CD34+CD7-sCD3-CD4-CD8-, and CD34+CD2-CD7- sCD3-CD4-CD8- subsets, indicating that T lymphocyte progenitors sensitive to signals mediated by thymic stroma in vitro are not restricted to CD34+ cells already coexpressing early T lymphocyte- associated markers. Finally, we show that T lymphopoiesis was enhanced by c-kit ligand.
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