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)-gamma(-) and IL-17(+)/IFN-gamma(+) subsets and expressed IL-23 receptor. Interestingly, IFN-gamma(+)TH-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.

Dander, E., Balduzzi, A., Zappa, G., Lucchini, G., Perseghin, P., André, V., et al. (2009). Interleukin-17-Producing T-Helper Cells as New Potential Player Mediating Graft-Versus-Host Disease in Patients Undergoing Allogeneic Stem-Cell Transplantation. TRANSPLANTATION, 88(11), 1261-1272 [10.1097/TP.0b013e3181bc267e].

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, A;LUCCHINI, GIOVANNA;ANDRÉ, VALENTINA ISABELLA;MIGLIAVACCA, MADDALENA;VILLA, ANTONELLO;BERTI, EMILIO;BIAGI, ETTORE;BIONDI, ANDREA;
2009

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)-gamma(-) and IL-17(+)/IFN-gamma(+) subsets and expressed IL-23 receptor. Interestingly, IFN-gamma(+)TH-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.
Articolo in rivista - Articolo scientifico
Scientifica
GvHD, Th-17, immunotherapy
English
1261
1272
12
http://www.ncbi.nlm.nih.gov/pubmed/19996925?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=2
Dander, E., Balduzzi, A., Zappa, G., Lucchini, G., Perseghin, P., André, V., et al. (2009). Interleukin-17-Producing T-Helper Cells as New Potential Player Mediating Graft-Versus-Host Disease in Patients Undergoing Allogeneic Stem-Cell Transplantation. TRANSPLANTATION, 88(11), 1261-1272 [10.1097/TP.0b013e3181bc267e].
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, P; Parma, M; Allavena, P; Biagi, E; Rovelli, A; Biondi, A; D'Amico, G
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/7876
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