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. 2020 May;50(5):725-735.
doi: 10.1002/eji.201948318. Epub 2020 Feb 10.

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

Olivier Hequet  1   2   3 , Audrey Nosbaum  1 , Aurélie Guironnet-Paquet  1 , Elisabeth Blasco  1 , Emmanuelle Nicolas-Virelizier  1 , Thomas S Griffith  4 , Dominique Rigal  3 , Fabrice Cognasse  3   5 , Jean-François Nicolas  1 , Marc Vocanson  1
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Free article

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

Olivier Hequet et al. Eur J Immunol. 2020 May.
Free article

Abstract

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.

Keywords: CD8+ regulatory T cells; T-cell priming; extracorporeal photochemotherapy; photopheresis; regulatory T cells.

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References

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