TY - JOUR
T1 - Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection
AU - Curci, Claudia
AU - Sallustio, Fabio
AU - Serino, Grazia
AU - De Palma, Giuseppe
AU - Trpevski, Mirko
AU - Fiorentino, Marco
AU - Rossini, Michele
AU - Quaglia, Marco
AU - Valente, Marialuisa
AU - Furian, Lucrezia
AU - Toscano, Alessia
AU - Mazzucco, Gianna
AU - Barreca, Antonella
AU - Bussolino, Stefania
AU - Gesualdo, Loreto
AU - Stratta, Piero
AU - Rigotti, Paolo
AU - Citterio, Franco
AU - Biancone, Luigi
AU - Schena, Francesco P.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - FFPE kidney biopsies
KW - chronic T cell-mediated rejection
KW - effector memory T cells
KW - transcriptomics
KW - FFPE kidney biopsies
KW - chronic T cell-mediated rejection
KW - effector memory T cells
KW - transcriptomics
UR - http://hdl.handle.net/10807/94119
U2 - 10.1093/ndt/gfw245
DO - 10.1093/ndt/gfw245
M3 - Article
SN - 0931-0509
VL - 31
SP - 2131
EP - 2142
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
ER -