Differentiation of myeloid dendritic cells into CD8α-positive dendritic cells in vivo

Abstract

Abstract Bone marrow-derived dendritic cells (DC) represent a family of antigen-presenting cells (APC) with varying phenotypes. For example, in mice, CD8α+ and CD8α− DC are thought to represent cells of lymphoid and myeloid origin, respectively. Langerhans cells (LC) of the epidermis are typical myeloid DC; they do not express CD8α, but they do express high levels of myeloid antigens such as CD11b and FcγR. By contrast, thymic DC, which derive from a lymphoid-related progenitor, express CD8α but only low levels of myeloid antigens. CD8α+ DC are also found in the spleen and lymph nodes (LN), but the origin of these cells has not been determined. By activating and labeling CD8α− epidermal LC in vivo, it was found that these cells expressed CD8α on migration to the draining LN. Similarly, CD8α− LC generated in vitro from a CD8 wild-type mouse and injected into the skin of a CD8αKO mouse expressed CD8α when they reached the draining LN. The results also show that CD8α+ LC are potent APC. After migration from skin, they localized in the T-cell areas of LN, secreted high levels of interleukin-12, interferon-γ, and chemokine-attracting T cells, and they induced antigen-specific T-cell activation. These results demonstrate that myeloid DC in the periphery can express CD8α when they migrate to the draining LN. CD8α expression on these DC appears to reflect a state of activation, mobilization, or both, rather than lineage.