Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Doan Ngoc TM

PROVIDER: S-EPMC9731633 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

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

Doan Ngoc Tra-My TM Tilly Gaëlle G Danger Richard R Danger Richard R Bonizec Orianne O Masset Christophe C Guérif Pierrick P Bruneau Sarah S Glemain Alexandre A Harb Jean J Cadoux Marion M Vivet Anaïs A Mai Hoa Le HL Garcia Alexandra A Laplaud David D Liblau Roland R Giral Magali M Blandin Stéphanie S Feyeux Magalie M Dubreuil Laurence L Pecqueur Claire C Cyr Matthew M Ni Weiming W Brouard Sophie S Degauque Nicolas N

Journal of the American Society of Nephrology : JASN 20221024 12

<h4>Background</h4>The mechanisms regulating CD8<sup>+</sup> T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8<sup>+</sup> T cells that re-express CD45RA (TEMRA CD8<sup>+</sup> T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection.<h4>Methods</h4>We used single-cell proteomic profiling and functional testing of CD8<sup>+</sup> T cell subsets to characterize thei ...[more]

PMID: 36280286

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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