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

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

doi:10.1093/ndt/gfw245

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

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

Department of Translational Medicine

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	2131-2142
Number of pages	12
Journal	Nephrology Dialysis Transplantation
Volume	31
Issue number	12
DOIs	https://doi.org/10.1093/ndt/gfw245
Publication status	Published - Dec 2016

Keywords

Chronic T cell-mediated rejection
Effector memory T cells
FFPE kidney biopsies
Transcriptomics

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10.1093/ndt/gfw245

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Curci, C., Sallustio, F., Serino, G., De Palma, G., Trpevski, M., Fiorentino, M., Rossini, M., Quaglia, M., Valente, M., Furian, L., Toscano, A., Mazzucco, G., Barreca, A., Bussolino, S., Gesualdo, L., Stratta, P., Rigotti, P., Citterio, F., Biancone, L., & Schena, F. P. (2016). Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection. Nephrology Dialysis Transplantation, 31(12), 2131-2142. https://doi.org/10.1093/ndt/gfw245

@article{6cc584b35df24902b10d58fa6ef95c1c,

title = "Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection",

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.",

keywords = "Chronic T cell-mediated rejection, Effector memory T cells, FFPE kidney biopsies, Transcriptomics",

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

note = "Publisher Copyright: {\textcopyright} The Author 2016.",

year = "2016",

month = dec,

doi = "10.1093/ndt/gfw245",

language = "English",

volume = "31",

pages = "2131--2142",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

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Curci, C, Sallustio, F, Serino, G, De Palma, G, Trpevski, M, Fiorentino, M, Rossini, M, Quaglia, M, Valente, M, Furian, L, Toscano, A, Mazzucco, G, Barreca, A, Bussolino, S, Gesualdo, L, Stratta, P, Rigotti, P, Citterio, F, Biancone, L & Schena, FP 2016, 'Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection', Nephrology Dialysis Transplantation, vol. 31, no. 12, pp. 2131-2142. https://doi.org/10.1093/ndt/gfw245

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 - 2016/12

Y1 - 2016/12

N2 - 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 - 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 - Chronic T cell-mediated rejection

KW - Effector memory T cells

KW - FFPE kidney biopsies

KW - Transcriptomics

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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

IS - 12

ER -

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

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Keywords

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