TEMRA CD8 T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2x4 Receptor-Dependent Proinflammatory and Migratory Responses
1Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France, 2University Hospital of Nantes, Nantes, France, 3CRTI- INSERM UMR 1064, Nantes, France, 4Nantes Université, Univ Angers, INSERM, CNRS, CRCINA, F-44000 Nantes, Nantes, France
Meeting: 2022 American Transplant Congress
Abstract number: 571
Keywords: Adhesion molecules, Kidney transplantation, T cells
Topic: Basic Science » Basic Clinical Science » 19 - Chronic Organ Rejection
Session Information
Session Name: Chronic Organ Rejection
Session Type: Rapid Fire Oral Abstract
Date: Tuesday, June 7, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 5:30pm-5:40pm
Location: Hynes Room 309
*Purpose: Whereas the role of effector memory and TEMRA CD8 in allotransplantation has been clearly evidenced and particularly the direct correlation between intragraft infiltrating CD8 and rejection, the mechanisms regulating the migration of CD8 T cells to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory (EM) re-expressing CD45RA (namely, TEMRA) CD8 are still unclear.
*Methods: Adhesion of EM and TEMRA CD8 from Kidney Transplant Recipient (KTx) and Healthy Volunteers (HV) to primary endothelial cell line, their transmigration, and time-lapse microscopy were used and the underlying mechanism was investigated using blocking antibodies and small inhibitory molecules. Activation (CD25, CD69; calcium flux) and cytotoxic function (CD107a) of EM and TEMRA CD8 were measured in response to chemokine CXCL12 stimulation and the role of purinergic receptor (P2XR1,4 and 7) were assessed.
*Results: Using static and dynamic models, we showed that after transplantation, the migratory fitness of TEMRA CD8 are enhanced compared to effector memory (EM) CD8, with enhanced adhesion to activated endothelium, a stronger ability to transmigrate across a monolayer of activated endothelial cells in response to CXCL12 and stronger patrolling behavior. In contrast, after transplantation, the migratory properties of TEMRA CD8 were very similar to those of TEMRA and EM CD8 purified from HV. Whereas the blockade of the interaction between functional PSGL1 and P-selectin prevent the adhesion and transmigration of TEMRA and EM CD8 from KTx, only TEMRA CD8 were susceptible to LFA-1 blockade. We found that the chemokine CXCL12 directly triggers a stimulatory signal involving an increase in cytosolic Ca2+ and a Panx1-dependent release of extracellular ATP, leading to autocrine stimulation of the purinergic receptor P2X4. Finally, we found that TEMRA CD8 from KTx exhibit a greater functional response as compared to EM CD8 upon CXCL12 stimulation
*Conclusions: Our findings suggest that therapeutic strategies such as LFA-1 blockade or impairing functional PGSL-1 could prevent TEMRA CD8 migration and activation and be directedly beneficial to patients with allotransplantation.
To cite this abstract in AMA style:
Tilly G, Doan-Ngoc T, Bonizec O, Masset C, Danger R, Guérif P, Bruneau S, Harb J, Giral M, Pecqueur C, Brouard S, Degauque N. TEMRA CD8 T Cells from Kidney Transplant Recipients Exhibit Enhanced Purinergic P2x4 Receptor-Dependent Proinflammatory and Migratory Responses [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/temra-cd8-t-cells-from-kidney-transplant-recipients-exhibit-enhanced-purinergic-p2x4-receptor-dependent-proinflammatory-and-migratory-responses/. Accessed May 6, 2025.« Back to 2022 American Transplant Congress