Molecular analysis identifies a specific role for memory effector T cells in kidney chronic T-cell mediated rejection

Chronic T-cell mediated rejection (TCMR) is characterized by the reduction of vessel lumen with marked intimal thickening, fibrous hyperplasia and a strong component of leukocyte infiltrate. Aim of our work was the study of gene expression profile in renal TCMR biopsies. We performed transcriptomics study using RNA extracted from archival formalin-fixed and paraffin-embedded (FFPE) renal biopsies obtained from patients with chronic and acute TCMR. Using a FC≥1.5 and a FDR<0.05, we identified 191 genes differentially expressed in patients with chronic and acute TCMR compared to cadaveric donor (CDs). The study of gene pathways showed the up-regulation of OX40 signaling, that is involved in the generation of memory effector T cell, and the up-regulation of KLRG-1, BLIMP-1 and CD25 that characterized CD8+ memory effector T cells. However, OX40 signaling was specific only for chronic TCMR. These results suggested the involvement of memory effector T cells in chronic TCMR. The identified genes may be used as a target for specific treatment of chronic TCMR. FFPE renal biopsies from 14 patients with chronic TCMR, 10 patients with acute TCMR and 52 cadaveric donors.