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

Transplantation. 2009 Dec 15;88(11):1261-72. doi: 10.1097/TP.0b013e3181bc267e.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Forkhead Transcription Factors / blood
  • Graft vs Host Disease / immunology*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Infant
  • Inflammation Mediators / blood
  • Interferon-gamma / blood
  • Interleukin-17 / blood*
  • Liver / immunology
  • Lymphocyte Count
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Receptors, Interleukin / blood
  • Skin / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology
  • Time Factors
  • Transplantation, Homologous
  • Young Adult


  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL23R protein, human
  • Inflammation Mediators
  • Interleukin-17
  • Receptors, Interleukin
  • Interferon-gamma