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

Olivier Hequet; Audrey Nosbaum; Aurélie Guironnet-Paquet; Elisabeth Blasco; Emmanuelle Nicolas-Virelizier; Thomas S. Griffith; Dominique Rigal; Fabrice Cognasse; Jean François Nicolas; Marc Vocanson

doi:10.1002/eji.201948318

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

Olivier Hequet, Audrey Nosbaum, Aurélie Guironnet-Paquet, Elisabeth Blasco, Emmanuelle Nicolas-Virelizier, Thomas S. Griffith, Dominique Rigal, Fabrice Cognasse, Jean François Nicolas, Marc Vocanson

Urology

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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⁺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.

Original language	English (US)
Pages (from-to)	725-735
Number of pages	11
Journal	European Journal of Immunology
Volume	50
Issue number	5
DOIs	https://doi.org/10.1002/eji.201948318
State	Published - May 1 2020

Bibliographical note

Funding Information:
The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytométrie 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.

Funding Information:
The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytométrie 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.

Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

CD8 regulatory T cells
T-cell priming
extracorporeal photochemotherapy
photopheresis
regulatory T cells

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

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",

author = "Olivier Hequet and Audrey Nosbaum and Aur{\'e}lie Guironnet-Paquet and Elisabeth Blasco and Emmanuelle Nicolas-Virelizier and Griffith, {Thomas S.} and Dominique Rigal and Fabrice Cognasse and Nicolas, {Jean Fran{\c c}ois} and Marc Vocanson",

note = "Funding Information: The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytom{\'e}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. Funding Information: The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytom{\'e}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. Publisher Copyright: {\textcopyright} 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

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doi = "10.1002/eji.201948318",

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T1 - CD8+ T cells mediate ultraviolet A-induced immunomodulation in a model of extracorporeal photochemotherapy

AU - Hequet, Olivier

AU - Nosbaum, Audrey

AU - Guironnet-Paquet, Aurélie

AU - Blasco, Elisabeth

AU - Nicolas-Virelizier, Emmanuelle

AU - Griffith, Thomas S.

AU - Rigal, Dominique

AU - Cognasse, Fabrice

AU - Nicolas, Jean François

AU - Vocanson, Marc

N1 - Funding Information: The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytométrie 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. Funding Information: The authors thank T. Andrieu and S. Dessurgey (Plateau technique de cytométrie 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. Publisher Copyright: © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2020/5/1

Y1 - 2020/5/1

N2 - 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.

AB - 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.

KW - CD8 regulatory T cells

KW - T-cell priming

KW - extracorporeal photochemotherapy

KW - photopheresis

KW - regulatory T cells

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