Expression of XCR1 Characterizes the Batf3-Dependent Lineage of Dendritic Cells Capable of Antigen Cross-Presentation.

ABSTRACT

Cross-presentation of antigen by dendritic cells (DCs) to CD8(+) T cells is a fundamentally important mechanism in the defense against pathogens and tumors. Due to the lack of an appropriate lineage marker, cross-presenting DCs in the mouse are provisionally classified as "Batf3-IRF-8-Id2-dependent DCs" or as "CD8(+) DCs" in the spleen, and as "CD103(+)CD11b(-) DCs" in the periphery. We have now generated a mAb to XCR1, a chemokine receptor which is specifically expressed on CD8(+) DCs and a subpopulation of double negative DCs in the spleen. Using this antibody, we have determined that only XCR1(+)CD8(+) (around 80% of CD8(+) DCs) and their probable precursors, XCR1(+)CD8(-) DCs, efficiently take up cellular material and excel in antigen cross-presentation. In lymph nodes (LNs) and peripheral tissues, XCR1(+) DCs largely, but not fully, correspond to CD103(+)CD11b(-) DCs. Most importantly, we demonstrate that XCR1(+) DCs in the spleen, LNs, and peripheral tissues are dependent on the growth factor Flt3 ligand and are selectively absent in Batf3-deficient animals. These results provide evidence that expression of XCR1 throughout the body defines the Batf3-dependent lineage of DCs with a special capacity to cross-present antigen. XCR1 thus emerges as the first surface marker characterizing a DC lineage in the mouse and potentially also in the human.