Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8alpha(-) and CD8alpha(+) dendritic cells are generated from CD4(low) lymphoid-committed precursors.

Two dendritic cell (DC) subsets have been identified in the murine system on the basis of their differential CD8alpha expression. CD8alpha(+) DCs and CD8alpha(-) DCs are considered as lymphoid- and myeloid-derived, respectively, because CD8alpha(+) but not CD8alpha(-) splenic DCs were generated from lymphoid CD4(low) precursors, devoid of myeloid reconstitution potential. Although CD8alpha(-) DCs were first described as negative for CD4, our results demonstrate that approximately 70% of them are CD4(+). Besides CD4(-) CD8alpha(-) and CD4(+) CD8alpha(-) DCs displayed a similar phenotype and T-cell stimulatory potential in mixed lymphocyte reaction (MLR), although among CD8alpha(-) 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 CD8alpha(+) DCs and CD8alpha(-) DCs were generated after transfer of CD4(low) precursors. These data suggest that both CD8alpha(+) and CD8alpha(-) DCs derive from a common precursor and, hence, do not support the concept of the CD8alpha(+) lymphoid-derived and CD8alpha(-) myeloid-derived DC lineages. However, because this hypothesis has to be confirmed at the clonal level, it remains possible that CD8alpha(-) DCs arise from a myeloid precursor within the CD4(low) precursor population or, alternatively, that both CD8alpha(+) and CD8alpha(-) DCs derive from an independent nonlymphoid, nonmyeloid DC precursor. In conclusion, although we favor the hypothesis that both CD8alpha(+) and CD8alpha(-) DCs derive from a lymphoid-committed precursor, a precise study of the differentiation process of CD8alpha(+) and CD8alpha(-) DCs is required to define conclusively their origin.

Langerhans cells develop from a lymphoid-committed precursor.

Langerhans cells (LCs) are specialized dendritic cells (DCs) strategically located in stratified epithelia, such as those of the skin, oral cavity, pharynx, esophagus, upper airways, urethra, and female reproductive tract, which are exposed to a wide variety of microbial pathogens. LCs play an essential role in the induction of T-lymphocyte responses against viruses, bacteria, and parasites that gain access to those epithelial surfaces, due to their high antigen capture and processing potential and their capacity to present antigen peptides to T cells on migration to the lymph nodes.(1) Although LCs have been classically considered of myeloid origin, recent reports, which demonstrate the existence of lymphoid DCs derived from multipotent lymphoid precursors devoid of myeloid differentiation potential,(2-5) raise the question of the lymphoid or myeloid origin of LCs. The present study shows that mouse lymphoid-committed CD4(low) precursors, with the capacity to generate T cells, B cells, CD8(+) lymphoid DCs, and natural killer cells,(26) also generate epidermal LCs on intravenous transfer, supporting the view that LCs belong to the lymphoid lineage. (Blood. 2000;96:1633-1637)

Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes, and skin of the mouse.

Dendritic cells (DC) are highly efficient antigen-presenting cells (APC) that have an essential function in the development of immune responses against microbial pathogens and tumors. Although during the past few years our understanding of DC biology has remarkably increased, a precise characterization of the different DC subpopulations remains to be achieved with regard to their phenotype and lineage relationships. In this report, we have extensively studied the DC subpopulations present in the thymus, spleen, Peyer's patches, lymph nodes (LN) and skin of the mouse. Thymus DC and 60% spleen DC have a lymphoid DC phenotype, ie, CD8(+) DEC-205(high) Mac-1(low), whereas 40% spleen DC have a myeloid DC phenotype, ie, CD8(-) DEC-205(low) Mac-1(high). Both CD8(+) and CD8(-) DC are leukocyte function-associated antigen-1 (LFA-1)high and highly adherent. Within Peyer's patches the majority of DC correspond to the CD8(+) DEC-205(high) Mac-1(low) lymphoid category. In the LN, together with CD8(+) and CD8(-) DC, an additional nonadherent CD8(int) LFA-1(int) subpopulation with lymphoid DC characteristics is described. Finally, in the skin both epidermal Langerhans cells (LC) and dermal DC are CD8(-)DEC-205(high) Mac-1 (high), and do not express LFA-1. Interestingly, LC migration experiments indicate that LC underwent the upregulation of CD8 and LFA-1 upon migration to the LN, supporting the hypothesis that LC belong to the CD8(+) lymphoid lineage.