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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3333-3341

PLENARY PAPER

Dendritic cell potentials of early lymphoid and myeloid progenitors

Markus G. Manz, David Traver, Toshihiro Miyamoto, Irving L. Weissman, and Koichi Akashi

From the Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA; and the Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA.

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.

© 2001 by The American Society of Hematology.
 

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