Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation

Erica Dander, Adriana Balduzzi, Greta Zappa, Giovanna Lucchini, Paolo Perseghin, Valentina André, Elisabetta Todisco, Daoud Rahal, Maddalena Migliavacca, Daniela Longoni, Graziella Solinas, Antonello Villa, Emilio Berti, Pamela Della Mina, Matteo Parma, Paola Allavena, Ettore Biagi, Attilio Rovelli, Andrea Biondi, Giovanna Dĝamico

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

OBJECTIVES: Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients. METHODS: Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA. RESULTS: An increased TH-17 population (up to 4.8% of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4%) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17/interferon (IFN)-γ3 and IL-17/IFN-γ3 subsets and expressed IL-23 receptor. Interestingly, IFN-γ3TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD. CONCLUSIONS: These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.

Original languageEnglish
Pages (from-to)1261-1272
Number of pages12
JournalTransplantation
Volume88
Issue number11
DOIs
Publication statusPublished - Dec 2009

Fingerprint

Interleukin-17
Stem Cell Transplantation
Graft vs Host Disease
Helper-Inducer T-Lymphocytes
Th17 Cells
Interferons
Hematopoietic Stem Cell Transplantation
Interleukin Receptors
Interleukin-23
Enzyme-Linked Immunospot Assay
Regulatory T-Lymphocytes
Confocal Microscopy
Autoimmune Diseases
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
Tissue Donors

Keywords

  • GVHD
  • TH-17 cells
  • Transplantation

ASJC Scopus subject areas

  • Transplantation

Cite this

Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation. / Dander, Erica; Balduzzi, Adriana; Zappa, Greta; Lucchini, Giovanna; Perseghin, Paolo; André, Valentina; Todisco, Elisabetta; Rahal, Daoud; Migliavacca, Maddalena; Longoni, Daniela; Solinas, Graziella; Villa, Antonello; Berti, Emilio; Mina, Pamela Della; Parma, Matteo; Allavena, Paola; Biagi, Ettore; Rovelli, Attilio; Biondi, Andrea; Dĝamico, Giovanna.

In: Transplantation, Vol. 88, No. 11, 12.2009, p. 1261-1272.

Research output: Contribution to journalArticle

Dander, E, Balduzzi, A, Zappa, G, Lucchini, G, Perseghin, P, André, V, Todisco, E, Rahal, D, Migliavacca, M, Longoni, D, Solinas, G, Villa, A, Berti, E, Mina, PD, Parma, M, Allavena, P, Biagi, E, Rovelli, A, Biondi, A & Dĝamico, G 2009, 'Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation', Transplantation, vol. 88, no. 11, pp. 1261-1272. https://doi.org/10.1097/TP.0b013e3181bc267e
Dander, Erica ; Balduzzi, Adriana ; Zappa, Greta ; Lucchini, Giovanna ; Perseghin, Paolo ; André, Valentina ; Todisco, Elisabetta ; Rahal, Daoud ; Migliavacca, Maddalena ; Longoni, Daniela ; Solinas, Graziella ; Villa, Antonello ; Berti, Emilio ; Mina, Pamela Della ; Parma, Matteo ; Allavena, Paola ; Biagi, Ettore ; Rovelli, Attilio ; Biondi, Andrea ; Dĝamico, Giovanna. / Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation. In: Transplantation. 2009 ; Vol. 88, No. 11. pp. 1261-1272.
@article{4a44ff72e8634f31a0f5e6dd14852b7d,
title = "Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation",
abstract = "OBJECTIVES: Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients. METHODS: Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA. RESULTS: An increased TH-17 population (up to 4.8{\%} of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4{\%}) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17/interferon (IFN)-γ3 and IL-17/IFN-γ3 subsets and expressed IL-23 receptor. Interestingly, IFN-γ3TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD. CONCLUSIONS: These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.",
keywords = "GVHD, TH-17 cells, Transplantation",
author = "Erica Dander and Adriana Balduzzi and Greta Zappa and Giovanna Lucchini and Paolo Perseghin and Valentina Andr{\'e} and Elisabetta Todisco and Daoud Rahal and Maddalena Migliavacca and Daniela Longoni and Graziella Solinas and Antonello Villa and Emilio Berti and Mina, {Pamela Della} and Matteo Parma and Paola Allavena and Ettore Biagi and Attilio Rovelli and Andrea Biondi and Giovanna Dĝamico",
year = "2009",
month = "12",
doi = "10.1097/TP.0b013e3181bc267e",
language = "English",
volume = "88",
pages = "1261--1272",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Interleukin-17-producing t-helper cells as new potential player mediating graft-versus-host disease in patients undergoing allogeneic stem-cell transplantation

AU - Dander, Erica

AU - Balduzzi, Adriana

AU - Zappa, Greta

AU - Lucchini, Giovanna

AU - Perseghin, Paolo

AU - André, Valentina

AU - Todisco, Elisabetta

AU - Rahal, Daoud

AU - Migliavacca, Maddalena

AU - Longoni, Daniela

AU - Solinas, Graziella

AU - Villa, Antonello

AU - Berti, Emilio

AU - Mina, Pamela Della

AU - Parma, Matteo

AU - Allavena, Paola

AU - Biagi, Ettore

AU - Rovelli, Attilio

AU - Biondi, Andrea

AU - Dĝamico, Giovanna

PY - 2009/12

Y1 - 2009/12

N2 - OBJECTIVES: Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients. METHODS: Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA. RESULTS: An increased TH-17 population (up to 4.8% of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4%) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17/interferon (IFN)-γ3 and IL-17/IFN-γ3 subsets and expressed IL-23 receptor. Interestingly, IFN-γ3TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD. CONCLUSIONS: These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.

AB - OBJECTIVES: Graft-versus-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem-cell transplantation, leading to significant mortality. Recently, T-helper (TH)-17 cells have been shown to play a central role in mediating several autoimmune diseases. The aim of our study was to investigate the relationship between TH-17 cells and GVHD occurring in transplanted patients. METHODS: Blood samples were collected from 51 hematopoietic stem-cell transplantation patients and 15 healthy donors. Patients with GVHD were monitored for the presence of TH-17 cells by ELISPOT or flow cytometry in the peripheral blood and by confocal microscopy in GVHD lesions. Cytokine plasma levels were detected by ELISA. RESULTS: An increased TH-17 population (up to 4.8% of peripheral blood CD4+T lymphocytes) was observed in patients with acute GVHD and (up to 2.4%) in patients with active chronic GVHD along with an inflammatory process. In contrast, the percentage of TH-17 cells drastically decreased in patients with inactive chronic GVHD. TH-17 cells consisted of both interleukin (IL)-17/interferon (IFN)-γ3 and IL-17/IFN-γ3 subsets and expressed IL-23 receptor. Interestingly, IFN-γ3TH-17 cells were able to infiltrate GVHD lesions as observed in liver and skin sections. Moreover, the proportion of TH-17 was inversely correlated with the proportion of regulatory T cells observed in the peripheral blood and tissues affected by GVHD. Finally, we demonstrated a strong correlation between TH-17 levels and the clinical status of patients with GVHD. CONCLUSIONS: These findings support the hypothesis that TH-17 are involved in the active phases of GVHD and may represent a novel cellular target for developing new strategies for GVHD treatment.

KW - GVHD

KW - TH-17 cells

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=73349105621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349105621&partnerID=8YFLogxK

U2 - 10.1097/TP.0b013e3181bc267e

DO - 10.1097/TP.0b013e3181bc267e

M3 - Article

C2 - 19996925

AN - SCOPUS:73349105621

VL - 88

SP - 1261

EP - 1272

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 11

ER -