Linkage between dendritic and T cell commitments in human circulating hematopoietic progenitors.

Kyoizumi S, Kubo Y, Kajimura J, Yoshida K, Hayashi T, Nakachi K, Young LF, Moore MA, van den Brink MR, Kusunoki Y
Source: J Immunol
Publication Date: (2014)
Issue: 192(12): 5749-60
Research Area:
Basic Research
Cells used in publication:
Mononuclear, bone marrow, human
Species: human
Tissue Origin: bone marrow
Mononuclear, cord blood, human
Species: human
Tissue Origin: blood
Mononuclear, peripheral blood, human
Species: human
Tissue Origin: blood
The relationships between commitments of dendritic cells (DCs) and T cells in human hematopoietic stem cells are not well understood. In this study, we enumerate and characterize conventional DC and plasmacytoid DC precursors in association with T cell and thymus-derived types of NK cell precursors among CD34(+) hematopoietic progenitor cells (HPCs) circulating in human peripheral blood. By limiting-dilution analyses using coculture with stroma cells expressing Notch1 ligand, the precursor frequencies (PFs) of DCs in HPCs were found to significantly correlate with T cell PFs, but not with NK cell PFs, among healthy donors. Clonal analyses showed that the majority of T/NK dual- and T single-lineage precursors-but only a minority of NK single-lineage precursors-were associated with the generation of DC progenies. All clones producing both DC and T cell progenies were found with monocyte and/or granulocyte progenies, suggesting DC differentiation via myeloid DC pathways. Analyses of peripheral blood HPC subpopulations revealed that the lineage split between DC and T/NK cell progenitor occurs at the stage prior to bifurcation into T and NK cell lineages. The findings suggest a strong linkage between DC and T cell commitments, which may be imprinted in circulating lymphoid-primed multipotent progenitors or in more upstream HPCs.