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+Teff). 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+TECP), which prevented the priming of CD8+Teff and the development of CHS, independently of conventional CD4+ regulatory T cells. CD8+TECP mediated tolerance by inhibiting the migration and functions of skin DC and subsequently the priming of CD8+Teff. CD8+TECP 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.
Bibliographical noteFunding Information:
The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytom?trie en flux, US8 / UMS3444 BioSciences Gerland - Lyon Sud) for their assistance with flow cytometry. The authors thank the SFHemapheresis (French Society of Hemapheresis) and the French National Blood Service ? EFS who partially financially supported this work.
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- CD8 regulatory T cells
- T-cell priming
- extracorporeal photochemotherapy
- regulatory T cells