Anatomic location and T-cell stimulatory functions of mouse dendritic cell subsets defined by CD4 and CD8 expression

Mouse spleen contains CD4(+), CD8alpha(+), and CD4(-)/CD8alpha(-) dendritic cells (DCs) in a 2:1:1 ratio. An analysis of 70 surface and cytoplasmic antigens revealed several differences in antigen expression between the 3 subsets. Notably, the Birbeck granule-associated Langerin antigen, as well as CD103 (the mouse homologue of the rat DC marker OX62), were specifically expressed by the CD8alpha(+) DC subset. All DC types were apparent in the T-cell areas as well as in the splenic marginal zones and showed similar migratory capacity in collagen lattices. The 3 DC sub-types stimulated allogeneic CD4(+) T cells comparably. However, CD8alpha(+) DCs were very weak stimulators of resting or activated allogeneic CD8(+) T cells, even at high stimulator-to-responder ratios, although this defect could be overcome under optimal DC/T cell ratios and peptide concentrations using CD8(+) F5 T-cell receptor (TCR)-transgenic T cells. CD8alpha(-) or CD8alpha(+) DCs presented alloantigens with the same efficiency for lysis by cytotoxic T lymphocytes (CTLs), and their turnover rate of class I-peptide complexes was similar, thus neither an inability to present, nor rapid loss of antigenic complexes from CD8alpha DCs was responsible for the low allostimulatory capacity of CD8alpha(+) DCs in vitro. Surprisingly, both CD8alpha(+) DCs and CD4(-)/CD8(-) DCs efficiently primed minor histocompatibility (H-Y male antigen) cytotoxicity following intravenous injection, whereas CD4(+) DCs were weak inducers of CTLs. Thus, the inability of CD8alpha(+) DCs to stimulate CD8(+) T cells is limited to certain in vitro assays that must lack certain enhancing signals present during in vivo Interaction between CD8alpha(+) DCs and CD8(+) T cells.