Concept of lymphoid versus myeloid dendritic cell lineages revisited:: both CD8α- and CD8α+ dendritic cells are generated from CD4low lymphoid-committed precursors

Two dendritic cell (DC) subsets have been identified in the murine system on the basis of their differential CD8 alpha expression. CD8 alpha(+) DCs and CD8 alpha(-) DCs are considered as lymphoid- and myeloid-derived, respectively, because CD8 alpha(+) but not CD8 alpha(-) splenic DCs were generated from lymphoid CD4(low) precursors, devoid of myeloid reconstitution potential. Although CD8 alpha(-) DCs were first described as negative for CD4, our results demonstrate that approximately 70% of them are CD4(+). Besides CD4(-) CD8 alpha(-) and CD4(+) CD8 alpha(-) DCs displayed a similar phenotype and T-cell stimulatory potential in mixed lymphocyte reaction (MLR), although among CD8 alpha(-) DCs, the CD4(+) subset appears to have a higher endocytic capacity. Finally experiments of DC reconstitution after irradiation in which, in contrast to previous studies, donor-type DCs were analyzed without depleting CD4(+) cells, revealed that both CD8 alpha(+) DCs and CD8 alpha(-) DCs were generated after transfer of CD4(low) precursors. These data suggest that both CD8 alpha(+) and CD8 alpha(-) DCs derive from a common precursor and, hence, do not support the concept of the CD8 alpha(+) lymphoid-derived and CD8 alpha(-) myeloid-derived DC lineages. However, because this hypothesis has to be confirmed at the clonal level, it remains possible that CD8 alpha(-) DCs arise from a myeloid precursor within the CD4(low) precursor population or, alternatively, that both CD8 alpha(+) and CD8 alpha(-) DCs derive from an independent nonlymphoid, nonmyeloid DC precursor. In conclusion, although we favor the hypothesis that both CD8 alpha(+) and CD8 alpha(-) DCs derive from a lymphoid-committed precursor, a precise study of the differentiation process of CD8 alpha(+) and CD8 alpha(-) DCs is required to define conclusively their origin. (Blood, 2000;96:2511-2519) (C) 2000 by The American Society of Hematology.