Identification of CD8α+CD11c− lineage phenotype-negative cells in the spleen as committed precursor of CD8α+ dendritic cells

Abstract

AbstractCD8α+ dendritic cells (DCs) represent a functionally distinct DC subset in vivo, which plays a critical role in initiating various cellular immune responses. However, the committed precursor of CD8α+ DCs remains to be identified. We reported here that murine splenic CD8α+CD11c− lineage phenotype (Lin)− cells could differentiate into CD8α+DCs in vivo after intravenous transplantation. Immunohistochemistry staining showed that donor-derived DCs mainly located in T-cell areas of the spleen. Functionally, these CD8α+CD11c−Lin− cell–derived DCs were capable of stimulating allogenic T-cell response, as well as secreting bioactive interleukin 12 p70 and interferon γ. Freshly isolated CD8α+CD11c−Lin− cells expressed CC chemokine receptor (CCR)2, CCR5, and CCR7 messenger RNA, whereas CD8α+ DCs derived from CD8α+CD11c−Lin− cells further obtained the expression of CCR6 and macrophage-derived chemokine. Flow cytometry analysis showed that CD8α+CD11c−Lin− cells were identified in bone marrow and lymph nodes. Moreover, transplanted splenic CD8α+CD11c−Lin− cells could also home to thymus and lymph nodes and were capable of developing into CD8α+ DCs in these locations. However, CD8α+CD11c−Lin−cells failed to differentiate into CD8α− DCs, T cells, natural killer cells, or other myeloid lineage cells in irradiated chimeras. Taken together, all these findings suggest that CD8α+CD11c−Lin− cells are a committed precursor of CD8α+ DCs.