Effector Memory-Expressing CD45RA (TEMRA) CD8 + T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2X4 Receptor-Dependent Proinflammatory and Migratory Responses.

Autor:	Doan Ngoc TM; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Tilly G; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Danger R; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Bonizec O; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Masset C; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Guérif P; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Bruneau S; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Glemain A; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Harb J; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Cadoux M; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Vivet A; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Mai HL; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Garcia A; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Laplaud D; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France., Liblau R; CNRS, Institut National de la Santé et de la Recherche Médicale, UPS, Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, Toulouse, France.; Department of Immunology, Toulouse University Hospital, Toulouse, France., Giral M; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Blandin S; CHU Nantes, CNRS, Institut National de la Santé et de la Recherche Médicale, BioCore, US16, SFR Bonamy, Nantes Université, Nantes, France., Feyeux M; CHU Nantes, CNRS, Institut National de la Santé et de la Recherche Médicale, BioCore, US16, SFR Bonamy, Nantes Université, Nantes, France., Dubreuil L; APEX PAnTher, INRAE, Oniris, Nantes, France., Pecqueur C; Université d'Angers, Institut National de la Santé et de la Recherche Médicale, CNRS, CRCI2NA, Nantes Université, Nantes, France., Cyr M; IsoPlexis Corporation, Branford, Connecticut., Ni W; IsoPlexis Corporation, Branford, Connecticut., Brouard S; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.; CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie, Nantes, France., Degauque N; Institut National de la Santé et de la Recherche Médicale, Nantes Université, CHU Nantes, Center for Research in Transplantation and Translational Immunology, UMR 1064, Nantes, France.
Jazyk:	angličtina
Zdroj:	Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2022 Dec; Vol. 33 (12), pp. 2211-2231. Date of Electronic Publication: 2022 Oct 24.
DOI:	10.1681/ASN.2022030286
Abstrakt:	Background: The mechanisms regulating CD8 + T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8 + T cells that re-express CD45RA (TEMRA CD8 + T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection. Methods: We used single-cell proteomic profiling and functional testing of CD8 + T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection. Results: We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8 + T cells in blood and kidney graft biopsies. TEMRA CD8 + T cells from kidney transplant recipients exhibited enhanced migratory properties compared with effector memory (EM) CD8 + T cells, with enhanced adhesion to activated endothelium and transmigration in response to the chemokine CXCL12. CXCL12 directly triggers a purinergic P2×4 receptor-dependent proinflammatory response of TEMRA CD8 + T cells from transplant recipients. The stimulation with IL-15 promotes the CXCL12-induced migration of TEMRA and EM CD8 + T cells and promotes the generation of functional PSGL1, which interacts with the cell adhesion molecule P-selectin and adhesion of these cells to activated endothelium. Although disruption of the interaction between functional PSGL1 and P-selectin prevents the adhesion and transmigration of both TEMRA and EM CD8 + T cells, targeting VLA-4 or LFA-1 (integrins involved in T cell migration) specifically inhibited the migration of TEMRA CD8 + T cells from kidney transplant recipients. Conclusions: Our findings highlight the active role of TEMRA CD8 + T cells in humoral transplant rejection and suggest that kidney transplant recipients may benefit from therapeutics targeting these cells. (Copyright © 2022 by the American Society of Nephrology.)
Databáze:	MEDLINE
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