Development of dendritic cells in culture from human and murine thymic precursor cells

The earliest T-precursor population in the adult murine thymus can give ris e to dendritic cells (DC) in culture if stimulated with a cocktail of cytok ines that includes interleukin (IL)-3, but not with cytokine mixes based on granulocyte-macrophage colony stimulating factor (GM-CSF), normally used t o generate myeloid-derived DC. This and other evidence led to the proposal that two different lineages of DC exist, one lymphoid-related and the other myeloid-related. To determine whether this selective response to cytokines was restricted to murine DC, early human thymic T-precursors were isolated and their capacity to generate DC in response to various cytokines directl y compared to their murine counterparts. In contrast to cultures of murine thymic precursors, CD34(+)CDla(-) lineage marker negative (Lin(-)) precurso r cells from the human thymus proliferated and generated DC with both the I L-3-containing cytokine mix lacking GM-CSF and with GM-CSF based cytokine m ixes. These CD34(+)CDla(-) Lin- human precursor cells also gave rise to NK cells under appropriate culture conditions, but produced no granulocyte, mo nocyte, eosinophil, megakaryocyte or erythroid cells in standard soft-agar colony-forming cell assays. Thus, although apparently lymphoid-restricted, the human thymic DC precursors responded to the myeloid factor GM-CSF as we ll as to the cytokines selective for murine lymphoid-related DC.