title: Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: C.A.R.S.O. Consortium, University of Bari, Bari, Italy.|Schena Foundation, Research Center of Renal Diseases, Bari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Curci
authors.affiliation: C.A.R.S.O. Consortium, University of Bari, Bari, Italy.|Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Sallustio
authors.affiliation: Laboratory of Experimental Immunopathology, IRCCS 'de Bellis', Castellana Grotte, Bari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Serino
authors.affiliation: C.A.R.S.O. Consortium, University of Bari, Bari, Italy.|Schena Foundation, Research Center of Renal Diseases, Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.affiliation: C.A.R.S.O. Consortium, University of Bari, Bari, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: Trpevski
authors.affiliation: Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fiorentino
authors.affiliation: Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Rossini
authors.affiliation: Nephrology and Kidney Transplant Unit, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.affiliation: Department of Cardiac, Thoracic and Vascular Sciences, Medical School, University of Padua, Padua, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Valente
authors.affiliation: Kidney Pancreas Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Furian
authors.affiliation: Renal Transplantation Unit, Department of Surgery, Catholic University, Rome, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Toscano
authors.affiliation: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Gianna
authors.initials: G
authors.lastname: Mazzucco
authors.affiliation: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Barreca
authors.affiliation: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bussolino
authors.affiliation: Renal, Dialysis and Transplant Unit, Department of Emergency and Organ Transplant, University of Bari, Bari, Italy.
authors.forename: Loreto
authors.initials: L
authors.lastname: Gesualdo
authors.affiliation: Nephrology and Kidney Transplant Unit, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Stratta
authors.affiliation: Kidney Pancreas Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.affiliation: Renal Transplantation Unit, Department of Surgery, Catholic University, Rome, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Citterio
authors.affiliation: Nephrology, Dialysis and Kidney Transplantation Unit, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Biancone
authors.affiliation: C.A.R.S.O. Consortium, University of Bari, Bari, Italy.|Schena Foundation, Research Center of Renal Diseases, Bari, Italy.
authors.forename: Francesco P
authors.initials: FP
authors.lastname: Schena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D053262:Receptors, OX40 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology; D055815:Young Adult
chemical_list: D053262:Receptors, OX40; C505716:TNFRSF4 protein, human
keywords: FFPE kidney biopsies; chronic T cell-mediated rejection; effector memory T cells; transcriptomics