Expression of CD86 on Human Marrow CD341 Cells Identifies Immunocompetent Committed Precursors of Macrophages and Dendritic Cells

Macrophages and dendritic cells derive from a hematopoietic stem cell and the existence of a common committed progenitor has been hypothesized. We have recently found in normal human marrow a subset of CD341 cells that constitutively expresses HLA-DR and low levels of CD86, a natural ligand for the T cell costimulation receptor CD28. This CD341 subset can elicit responses from allogeneic T cells. In this study, we show that CD341/CD861 cells can also present tetanus toxoid antigen to memory CD41 T cells. CD86 is expressed at low levels in macrophages and high levels in dendritic cells. Therefore, we have tested the hypothesis that CD341/CD861 cells are the common precursors of both macrophages and dendritic cells. CD341/CD861 marrow cells cultured in granulocyte-macrophage colonystimulating factor (GM-CSF)–generated macrophages. In contrast, CD341/CD862 cells cultured in GM-CSF generated a predominant population of granulocytes. CD341/CD861 cells cultured in GM-CSF plus tumor necrosis factor-a (TNF-a) generated almost exclusively CD1a1/CD831 dendritic cells. In contrast, CD341/CD862 cells cultured in GM-CSF plus TNF-a generated a variety of cell types, including a small population of dendritic cells. In addition, CD341/CD861 cells cultured in granulocyte colony-stimulating factor failed to generate CD151 granulocytes. Therefore, CD341/CD861 cells are committed precursors of both macrophages and dendritic cells. The ontogeny of dendritic cells was recapitulated by stimulation of CD341/CD862 cells with TNF-a that induced expression of CD86. Subsequent costimulation of CD861 cells with GM-CSF plus TNF-a lead to expression of CD83 and produced terminal dendritic cell differentiation. Thus, expression of CD86 on hematopoietic progenitor cells is regulated by TNF-a and denotes differentiation towards the macrophage or dendritic cell lineages. r 1998 by The American Society of Hematology.