Archive des Bibliothèques universitaires de Nantes

The Characterization of CD8 T Lymphocyte Subset Differentiation and Their Immunometabolic Programming in Kidney Transplantation

Par : Yap, Michelle

Document archivé le : 28/04/2016

Despite the advancements in immunosuppresssion therapy, long term allograft dysfunction is still a main barrier to successful kidney transplantation. Therefore, biomarkers that can guide patient care are important to extending the life of a kidney allograft. The aim of this thesis was to investigate the role of CD8 T cells in kidney transplant patients, evaluate the use of these cells as possible biomarkers, and to examine the metabolic programming and machinery used by these cells in healthy volunteers and transplant patients. Kidney transplant patients who have stable graft function one year post-transplantation and have an increased frequency of late-differentiated TEMRA CD8 T cells were more at risk of late graft dysfunction compared to stable kidney transplant recipients with lower levels of these cells. Furthermore, using CD8 cells as biomarkers and additional parameters in a revised Kidney Transplant Failure Score (KTFS) resulted in better classification of at-risk patients. We also compared the metabolic machinery used by TEMRA CD8 cells to those of naive and effector memory (EM) CD8 subsets. In healthy volunteers, EM and TEMRA cells have higher basal glycolytic activity compared to naive cells, and after activation, EM and TEMRA can sustain higher levels of glycolysis and mitochondrial respiration compared to naive cells. Additionally, TEMRA and EM cells have a higher basal concentration of stored ATP. Furthermore, glycolysis and glutaminolysis are essential for CD8 production of proinflammatory cytokines. Overall, these results show that the immunometabolic properties of CD8 T cells have a promising role. 15NANT22-VS

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