Dendritic cell potentials of early lymphoid and myeloid progenitors.
It has been proposed that there are at least 2 classes of dendritic cells (DCs), CD8alpha(+) DCs derived from the lymphoid lineage and CD8alpha(-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their overall contributions to the DC compartment are evaluated. It has previously been shown that primitive myeloid-committed progenitors (common myeloid progenitors [CMPs]) are efficient precursors of both CD8alpha(+) and CD8alpha(-) DCs in vivo. Here it is shown that the earliest lymphoid-committed progenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny granulocyte-macrophage progenitors (GMPs) can give rise to functional DCs in vitro and in vivo. CLPs are more efficient in generating DCs than their T-lineage descendants, the early thymocyte progenitors and pro-T cells, and CMPs are more efficient DC precursors than the descendant GMPs, whereas pro-B cells and megakaryocyte-erythrocyte progenitors are incapable of generating DCs. Thus, DC developmental potential is preserved during T- but not B-lymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP. In vivo reconstitution experiments show that CLPs and CMPs can reconstitute CD8alpha(+) and CD8alpha(-) DCs with similar efficiency on a per cell basis. However, CMPs are 10-fold more numerous than CLPs, suggesting that at steady state, CLPs provide only a minority of splenic DCs and approximately half the DCs in thymus, whereas most DCs, including CD8alpha(+) and CD8alpha(-) subtypes, are of myeloid origin. (Blood. 2001;97:3333-3341)
Manz
M G
MG
Department of Pathology, Stanford University School of Medicine, 279 Campus Dr., Stanford, CA 94305-5428, USA. manz@leland.stanford.edu
Traver
D
D
Miyamoto
T
T
Weissman
I L
IL
Akashi
K
K
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000166:cytology; D016827:CD8 Antigens / Q000032:analysis; D002452:Cell Count; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D015672:Erythroid Precursor Cells / Q000166:cytology; D006098:Granulocytes; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D008214:Lymphocytes; D008264:Macrophages / Q000166:cytology; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D016827:CD8 Antigens