Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Franco Citterio, Marialuisa Valente, Claudia Curci, Fabio Sallustio, Grazia Serino, Giuseppe De Palma, Mirko Trpevski, Marco Fiorentino, Michele Rossini, Marco Quaglia, Lucrezia Furian, Gianna Mazzucco, Antonella Barreca, Stefania Bussolino, Loreto Gesualdo, Piero Stratta, Paolo Rigotti, Luigi Biancone, Francesco P. Schena

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Abstract BACKGROUND: Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies. METHODS: RNA extracted from archival formalin-fixed, paraffin-embedded renal biopsies was used for gene expression profiling. Our study included 14 patients with chronic TCMR and 10 with acute TCMR. Fifty-two cadaveric donors were used as controls. The results were validated in an independent set of kidney biopsies. RESULTS: We identified 616 and 243 differentially expressed genes with a fold change ≥1.5 and a false discovery rate <0.05 in chronic and acute TCMR, respectively. Pathway analysis revealed upregulation of OX40 signalling. This pathway is involved in the generation of CD8+ effector memory T cells and the upregulation of killer cell lectin-like receptor G1 (KLRG-1), B lymphocyte-induced maturation protein 1 (BLIMP-1) and CD25, which characterize CD8+ effector memory T cells. However, the enhanced OX40 signalling pathway was specific to chronic TCMR; a significant increase of KLRG-1+/CD8+ and BLIMP-1+/CD8+ was only detected in these specimens. CONCLUSIONS: These results suggest the involvement of memory-committed CD8+ effector T cells in chronic TCMR. The generation of effector memory T cells is mediated by the OX40 gene pathway, and could be considered a future target for the specific treatment of chronic TCMR.
Original languageEnglish
Pages (from-to)2131-2142
Number of pages12
JournalNephrology Dialysis Transplantation
Volume31
DOIs
Publication statusPublished - 2016

Keywords

  • FFPE kidney biopsies
  • chronic T cell-mediated rejection
  • effector memory T cells
  • transcriptomics

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