| 초록 |
In this study, we investigated the role of T cells in renal transplant rejection, focusing on their abundance and metabolic activity. T cell mediated transplant rejection patients (N=40) were enrolled in the study; all were biopsy proven, Control were transplant patients with stable graft function (N=40). The T cell markers in the PBMCs were evaluated by flowcytometry, the metabolic status of T cells was studied using the SCNIETH assay. Gene expression analysis was studied using qPCR. Our findings reveal a marked increase in the percentage of T cells infiltrating the grafts during episodes of rejection compared to non-rejecting controls (Th1, Th2, Th17, Tregs, in all subtypes p<0.0001). These T cells exhibited enhanced bioenergetics (glycolysis 84%, OXPHOS 27%), characterized by elevated oxidative phosphorylation and glycolysis (p<0.001), suggesting a metabolic reprogramming that supports their heightened proliferative and effector functions. This metabolic shift correlates with increased expression of key transcription factors (T bet, GATA3, FOXP3, ROR Gamma T, p<0.001) and cytokines involved in T cell activation and differentiation (IFN-gamma, IL-17, IL4 p<0.0001). AMPK1 was observed to be the master regulator, and the gene expression was reduced in transplant biopsies (p<0.001). Our results highlight the importance of T cell metabolism in the pathogenesis of TCMR and suggest that targeting metabolic pathways may offer a novel approach to modulate T cell activity and improve graft survival. These findings provide new insights into the cellular and metabolic dynamics of T cell-mediated renal transplant rejection and open avenues for the development of metabolic interventions in transplant immunology. |