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

CD8alpha(+) 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 CD8alpha(+) DCs remains to be identified. We reported here that murine splenic CD8alpha(+)CD11c(-)lineage phenotype (Lin)(-) cells could differentiate into CD8alpha(+) DCs in vivo after intravenous transplantation. lmmunohistochemistry staining showed that donor-derived DCs mainly located in T-cell areas of the spleen. Functionally, these CD8alpha(+)CD11c(-)Lin(-)cell-derived DCs were capable of stimulating allogenic T-cell response, as well as secreting bioactive interleukin 12 p70 and interferon-gamma. Freshly isolated CD8alpha(+)CD11c(-)Lin(-) cells expressed CC chemokine receptor (CCR)2, CCR5, and CCR7 messenger RNA, whereas CD8alpha(+) DCs derived from CD8alpha(+)CD11c(-)Lin(-) cells further obtained the expression of CCR6 and macrophage-derived chemokine. Flow cytometry analysis showed that CD8alpha(+)CD11c(-)Lin(-) cells were identified in bone marrow and lymph nodes. Moreover, transplanted splenic CD8a+CD11 c-Lin- cells could also home to thymus and lymph nodes and were capable of developing into CD8alpha(+) DCs in these locations. However, CD8alpha(+)CD11c(-)Lin(-)cells failed to differentiate into CD8alpha(-) DCs, T cells, natural killer cells, or other myeiold lineage cells in irradiated chimeras. Taken together, all these findings suggest that CD8alpha(+)CD11c(-)Lin(-) cells are a committed precursor of CD8alpha(+) DCs.