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.
Martín
P
P
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain.
del Hoyo
G M
GM
Anjuère
F
F
Ruiz
S R
SR
Arias
C F
CF
Marín
A R
AR
Ardavín
C
C
D000818:Animals; D015703:Antigens, CD; D015704:CD4 Antigens / Q000032:analysis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D006098:Granulocytes / Q000166:cytology* / Q000276:immunology; D007700:Kinetics; D051917:Leukosialin; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012795:Sialoglycoproteins / Q000276:immunology / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology
D015703:Antigens, CD; D015704:CD4 Antigens; D019013:CD40 Antigens; D016827:CD8 Antigens; D051917:Leukosialin; D012795:Sialoglycoproteins; C497863:Spn protein, mouse