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.