DEC-205 as a marker of dendritic cells with regulatory effects on CD8 T cell responses

Abstract

We have previously reported that a population of lymphoid-related CD8α+ DEC-205+ dendritic cells (DC) from mouse spleen have 'regulatory' effects on the T cells they activate. CD8 T cells produce IL-2 and give a sustained proliferative response to allogeneic CD8α- DEC-205- splenic DC, but produce little IL-2 and give a limited response to allogeneic CD8+ DEC-205+ splenic DC. Although CD8α and DEC-205 correlate closely among splenic DC, lymph nodes (LN) include a large population of CD8α(low) DEC-205(high) DC. By i.v. transfer of purified thymic early lymphoid precursors into irradiated recipient mice we now demonstrate that these CD8α(low) but DEC-205(high) LN DC can be the progeny of a lymphoid precursor population, apparently corresponding to the CD8α(high) DEC-205(high) DC progeny of the same precursors in spleen and thymus. By culture of the separated, purified DC with allogeneic CD8 T cells we demonstrate that the CD8α(low) DEC-205(high) DC of LN are also functionally equivalent to the CD8α(high) DEC-205(high) DC of spleen. Therefore, DEC-205 but not CD8α serves to segregate functionally distinct DC types in LN. However, DC isolated from the spleens of genetically manipulated DEC-205(null) mice and separated on the basis of CD8α expression have a similar capacity to stimulate CD8 T cells as their heterozygous littermate controls, with the CD8α+ but now DEC-205(null) DC still giving restricted responses. In conclusion, high expression of DEC-205 appears to be a good marker of the lymphoid-related regulatory type of DC, but DEC-205 itself is not responsible for transmitting negative signals to the T cells.