CD8⁺ T cells mediate ultraviolet A-induced immunomodulation in a model of extracorporeal photochemotherapy

Extracorporeal photochemotherapy (ECP) that takes advantage of the immunomodulatory effects of UV light has been extensively used for many years for the treatment of several T cell-mediated diseases, including graft-versus-host disease (GvHD) and systemic scleroderma. Immune mechanisms that lead to the establishment of T cell tolerance in ECP-treated patients remain poorly known. In this study, we have tested the effect of UV/psoralen-treated BM-derived dendritic cells, referred to as ECP-BMDCs on the outcome of an antigen-specific T cell-mediated reaction, that is, contact hypersensitivity (CHS), which is mediated by CD8⁺ effector T cells (CD8⁺ T_eff ). The intravenous (i.v.) injection of antigen-pulsed ECP-BMDCs in recipient C57BL/6 mice induced specific CD8⁺ T cells endowed with immunomodulatory properties (referred to as CD8⁺ T_ECP ), which prevented the priming of CD8⁺ T_eff and the development of CHS, independently of conventional CD4⁺ regulatory T cells. CD8⁺ T_ECP mediated tolerance by inhibiting the migration and functions of skin DC and subsequently the priming of CD8⁺ T_eff . CD8⁺ T_ECP displayed none of the phenotypes of the usual CD8⁺ T regulatory cells described so far. Our results reveal an underestimated participation of CD8⁺ T cells to ECP-induced immunomodulation that could explain the therapeutic effects of ECP in T cell-mediated diseases.