Polak, Marta E., Newell, Louise, Taraban, Vadim Y., Pickard, Christopher, Healy, Eugene, Friedmann, Peter S., Al-Shamkhani, Aymen and Ardern-Jones, Michael R.
CD70-CD27 interaction augments CD8+ T-Cell activation by human epidermal langerhans cells
Journal of Investigative Dermatology, 132, (6), . (doi:10.1038/jid.2012.26). (PMID:22377764).
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Human cutaneous dendritic cells (DCs) from epidermal and dermal compartments exhibit functional differences in their induction of CD4+ T-cell and humoral immune responses; however, differences in the regulation of memory CD8+ T-cell responses by human skin DCs remain poorly characterized. We tested the capacity of human Langerhans cells (LCs) and dermal dendritic cells (DDCs) to induce antigen-specific cytokine production and proliferation of memory CD8+ cells. Although tumor necrosis factor-?-matured human DCs from both epidermal and dermal compartments showed efficient potential to activate CD8+ cells, LCs were constitutively more efficient than DDCs in cross-presenting CD8+ epitopes, as well as direct presentation of viral antigen to Epstein-Barr virus-specific CD8+ T cells. LCs showed greater expression of CD70, and blockade of CD70-CD27 signaling demonstrated that superiority of CD8+ activation by epidermal LC is CD70 dependent. This CD70-related activation of CD8+ cells by LCs denotes a central role of LCs in CD8+ immunity in skin, and suggests that regulation of LC CD70 expression is important in enhancing immunity against cutaneous epithelial pathogens and cancer.
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