Phenotypic switch of CD8(+) T cells reactivated under hypoxia toward IL-10 secreting, poorly proliferative effector cells

Article Article scientifique Article Phenotypic switch of CD8(+) T cells reactivated under hypoxia toward IL-10 secreting, poorly proliferative effector cells eng 2015 author Vuillefroy De Silly Romain 782322 author Ducimetiere Laura 761376 author Yacoub Maroun Céline 656899 author Dietrich Pierre-Yves 96532 author Derouazi Madiha Sabiha 83271 author Walker Paul Richard 0000-0001-8999-6366 104900 2263-2275 10.1002/eji.201445284 25929785 0014-2980 CD8(+) T cells controlling pathogens or tumors must function at sites where oxygen tension is frequently low, and never as high as under atmospheric culture conditions. However, T-cell function in vivo is generally analyzed indirectly, or is extrapolated from in vitro studies under nonphysiologic oxygen tensions. In this study, we delineate the role of physiologic and pathologic oxygen tension in vitro during reactivation and differentiation of tumor-specific CD8(+) T cells. Using CD8(+) T cells from pmel-1 mice, we observed that the generation of CTLs under 5% O2, which corresponds to physioxia in lymph nodes, gave rise to a higher effector signature than those generated under atmospheric oxygen fractions (21% O2). Hypoxia (1% O2) did not modify cytotoxicity, but decreasing O2 tensions during CTL and CD8(+) tumor-infiltrating lymphocyte reactivation dose-dependently decreased proliferation, induced secretion of the immunosuppressive cytokine IL-10, and upregulated the expression of CD137 (4-1BB) and CD25. Overall, our data indicate that oxygen tension is a key regulator of CD8(+) T-cell function and fate and suggest that IL-10 release may be an unanticipated component of CD8(+) T cell-mediated immune responses in most in vivo microenvironments. Animals Antigens, CD137/genetics/immunology CD8-Positive T-Lymphocytes/immunology/pathology Cell Hypoxia/genetics/immunology Cell Line, Tumor Cell Proliferation Humans Interleukin-10/genetics/immunology Interleukin-2 Receptor alpha Subunit/genetics/immunology Mice Mice, Transgenic Neoplasms, Experimental/genetics/immunology/pathology Dewey 616 56 Département de médecine 221 false 401 Immunobiologie des tumeurs du cerveau 669 27 Immunothérapie des cancers 42 European Journal of Immunology 45 8 8ad72dd5-f2f7-4d75-9e3d-b5b90a5256c9 Article (Published version) Restricted Vuillefroy-de-Silly_et_al-2015-European_Journal_of_Immunology.pdf 1560977 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Phenotypic switch of CD8(+) T cells reactivated under hypoxia toward IL-10 secreting, poorly proliferative effector cells	European Journal of Immunology			2015	557	7

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Ducimetiere, Laura