Linkage between dendritic and T cell commitments in human circulating hematopoietic progenitors.
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.
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan; kyoizumi@rerf.or.jp.
Seishi
S
Kyoizumi
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan;
Yoshiko
Y
Kubo
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan;
Junko
J
Kajimura
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan;
Kengo
K
Yoshida
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan;
Tomonori
T
Hayashi
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan;
Kei
K
Nakachi
Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and.
Lauren F
LF
Young
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065.
Malcolm A
MA
Moore
Department of Medicine and Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065; and.
Marcel R M
MR
van den Brink
Department of Radiobiology/Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima 732-0815, Japan;
Yoichiro
Y
Kusunoki
D000818:Animals; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology*; D051881:Receptor, Notch1 / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
C497761:NOTCH1 protein, human; D051881:Receptor, Notch1