Dendritic cell potentials of early lymphoid and myeloid progenitors

It has been proposed that there are at least 2 classes of dendritic cells ( DCs), CD8 alpha (+) DCs derived from the lymphoid lineage and CD8 alpha (-) DCs derived from the myeloid lineage. Here, the abilities of lymphoid- and myeloid-restricted progenitors to generate DCs are compared, and their ove rall contributions to the DC compartment are evaluated. It has previously b een shown that primitive myeloid-committed progenitors (common myeloid prog enitors [CMPs]) are efficient precursors of both CD8 alpha (+) and CD8 alph a (-) DCs in vivo. Here it is shown that the earliest lymphoid-committed pr ogenitors (common lymphoid progenitors [CLPs]) and CMPs and their progeny g ranulocyte-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 C MPs are more efficient DC precursors than the descendant GMPs, whereas pro- B cells and megakaryocyte-erythrocyte progenitors are incapable of generati ng DCs, Thus, DC developmental potential is preserved during T- but not B-l ymphoid differentiation from CLP and during granulocyte-macrophage but not megakaryocyte-erythrocyte development from CMP In vivo reconstitution exper iments show that CLPs and CMPs can reconstitute CD8 alpha (+) and CD8 alpha (-) 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, w hereas most DCs, including CD8 alpha (+) and CD8 alpha (-) subtypes, are of myeloid origin. (Blood, 2001;97:3333-3341) (C) 2001 by The American Societ y of Hematology.