Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease

Blood. 2008 Sep 1;112(5):2101-10. doi: 10.1182/blood-2007-12-126987. Epub 2008 Jul 2.


Th17 is a newly identified T-cell lineage that secretes proinflammatory cytokine IL-17. Th17 cells have been shown to play a critical role in mediating autoimmune diseases such as EAE, colitis, and arthritis, but their role in the pathogenesis of graft-versus-host disease (GVHD) is still unknown. Here we showed that, in an acute GVHD model of C57BL/6 (H-2(b)) donor to BALB/c (H-2(d)) recipient, IL-17(-/-) donor T cells manifested an augmented Th1 differentiation and IFN-gamma production and induced exacerbated acute GVHD. Severe tissue damage mediated by IL-17(-/-) donor T cells was associated with increased Th1 infiltration, up-regulation of chemokine receptors by donor T cells, and enhanced tissue expression of inflammatory chemokines. Administration of recombinant IL-17 and neutralizing IFN-gamma in the recipients given IL-17(-/-) donor cells ameliorated the acute GVHD. Furthermore, the regulation of Th1 differentiation by IL-17 or Th17 may be through its influence on host DCs. Our results indicate that donor Th17 cells can down-regulate Th1 differentiation and ameliorate acute GVHD in allogeneic recipients, and that treatments neutralizing proinflammatory cytokine IL-17 may augment acute GVHD as well as other inflammatory autoimmune diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Chemokines / genetics
  • DNA Primers / genetics
  • Gene Expression
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / genetics
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Interferon-gamma / antagonists & inhibitors
  • Interleukin-17 / administration & dosage
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / deficiency
  • Interleukin-17 / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutralization Tests
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / pathology*
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • Th1 Cells / immunology*
  • Th1 Cells / pathology*
  • Tissue Donors
  • Transplantation, Homologous


  • Chemokines
  • DNA Primers
  • Interleukin-17
  • Interferon-gamma