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EARLY EXPANSION OF TEMRA CD8 WITH INNATE-LIKE FUNCTION IDENTIFIES KIDNEY TRANSPLANT RECIPIENTS AT HIGH-RISK OF GRAFT FAILURE
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Lola Jacquemont and Gaëlle Tilly are co-authors. International audience. 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 characterize the 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 vitro Antibody 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.
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