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Transplantation
Oral
Lola Jacquemont, MD, PhD
CRTI UMR1064, INSERM, Université de Nantes
Gaelle Tilly
Engineer
CRTI UMR1064, INSERM, Université de Nantes
Michelle Yap, PhD
CRTI UMR1064, INSERM, Université de Nantes
Tra My Doan Ngoc
PhD student
CRTI UMR1064, INSERM, Université de Nantes
Richard Danger
post-doctorate
CRTI UMR1064, INSERM, Université de Nantes
Pierrick Guerif
Institut de Transplantation Urologie Néphrologie (ITUN), CHU Nantes
Florent Delbos, PhD
Laboratoire HLA, Etablissement Français du Sang Centre Pays-de-le-Loire
Bernard Martinet
CRTI UMR1064, INSERM, Université de Nantes
Magali Giral, MD, PhD
PU-PH
CRTI UMR1064, INSERM, Université de Nantes
Yohann Foucher, PhD
SPHERE UMR1246, INSERM, Université de Nantes
Sophie Brouard, DVM, PhD
Centre de Recherche en Transplantation et Immunologie (CRTI) UMR 1064, INSERM, Université de Nantes, ITUN, CHU de Nantes
Nicolas Degauque, PhD
Research Scientist
CRTI UMR1064, INSERM, Université de Nantes
As CD8 TEMRA cells are associated with higher risk of long-term graft dysfunction, in this study, we evaluate if the monitoring of CD8-related biomarkers could improve the prognostic capacities of a clinical-based scoring system (Kidney Transplant Failure Score; KTFS). We also characterizethe functionality of TEMRA and especially their reactivity upon donor-specific stimulation. 286 kidney-transplant recipients prospectively enrolled were followed for more than 8-years. 51 return in dialysis. We demonstrate that the frequency of early memory CD8 cells (EM) and TEMRA measured at 1-year post-transplantation is correlated with the risk to return in dialysis during time. For patients at high-risk of long-term graft dysfunction (according to KTFS), the use of one-year TEMRA frequency allows the discrimination of patients that will lose their graft from those that will not. Donor-specific reactivities from TEMRA and EM were similar with an early expression of CD25+CD69+CD107a+and the high secretion of pro-inflammatory and cytotoxic molecules. Importantly, we identify an innate-like signature of TEMRA, with more than 5-fold higher expression of FCGR3A (CD16) by TEMRA as compared to NAIVE and EM. Cross-linking of CD16 triggers the secretion of TNFa and IFNg by TEMRA and their cytotoxic function and was further enhanced by the provision of IL-15. Finally, we demonstrate TEMRA and not EM display in vitroAntibody Dependent Cell Cytotoxicity conferring to TEMRA features of both adaptive and innate-like immunity and showing that anti-HLA antibodies, a major risk factor for long-term allograft outcome, could activate TEMRA in a TCR-independent manner leading to the inflammatory response.