Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8α− and CD8α+dendritic cells are generated from CD4lowlymphoid-committed precursors

Two dendritic cell (DC) subsets have been identified in the murine system on the basis of their differential CD8α expression. CD8α+ DCs and CD8α− DCs are considered as lymphoid- and myeloid-derived, respectively, because CD8α+ but not CD8α− splenic DCs were generated from lymphoid CD4low precursors, devoid of myeloid reconstitution potential. Although CD8α− DCs were first described as negative for CD4, our results demonstrate that approximately 70% of them are CD4+. Besides CD4− CD8α− and CD4+CD8α− DCs displayed a similar phenotype and T-cell stimulatory potential in mixed lymphocyte reaction (MLR), although among CD8α− 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 CD8α+ DCs and CD8α− DCs were generated after transfer of CD4low precursors. These data suggest that both CD8α+ and CD8α− DCs derive from a common precursor and, hence, do not support the concept of the CD8α+ lymphoid-derived and CD8α−myeloid-derived DC lineages. However, because this hypothesis has to be confirmed at the clonal level, it remains possible that CD8α− DCs arise from a myeloid precursor within the CD4low precursor population or, alternatively, that both CD8α+ and CD8α− DCs derive from an independent nonlymphoid, nonmyeloid DC precursor. In conclusion, although we favor the hypothesis that both CD8α+ and CD8α− DCs derive from a lymphoid-committed precursor, a precise study of the differentiation process of CD8α+ and CD8α− DCs is required to define conclusively their origin.