IFN-γ receptor-deficient donor T cells mediate protection from graft-versus-host disease and preserve graft-versus-tumor responses after allogeneic bone marrow transplantation.

نویسندگان

  • Kai Sun
  • Hui-Hua Hsiao
  • Minghui Li
  • Erik Ames
  • Myriam Bouchlaka
  • Lisbeth A Welniak
  • Takeshi Hagino
  • Jared Jagdeo
  • Chien-Chun Pai
  • Mingyi Chen
  • Bruce R Blazar
  • Mehrdad Abedi
  • William J Murphy
چکیده

Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. It has been previously reported that lung GVHD severity directly correlates with the expansion of donor Th17 cells in the absence of IFN-γ. However, the consequence of Th17-associated lung GVHD in the presence of IFN-γ has not been well characterized. In the current study, T cells from IFN-γ receptor knockout (IFN-γR(-/-)) mice, capable of producing IFN-γ but unable to signal in response to IFN-γ, have been used to elucidate further the role of IFN-γ in GVHD. We found the transfer of donor T cells from either IFN-γR(-/-) or IFN-γ knockout (IFN-γ(-/-)) mice resulted in significant increases in donor Th17 cells in the lung. Marked increases in IL-4-producing Th2 cells infiltrating the lungs were also observed in the mice of donor IFN-γR(-/-) T cells. Notably, despite the presence of these cells, these mice did not show the severe immune-mediated histopathological lung injury observed in mice receiving donor IFN-γ(-/-) T cells. Increases in lung GVHD did occur in mice with donor IFN-γR(-/-) T cells when treated in vivo with anti-IFN-γ demonstrating that the cytokine has a protective role on host tissues in GVHD. A survival benefit from acute GVHD was also observed using donor cells from IFN-γR(-/-) T cells compared with control donors. Importantly, tumor-bearing mice receiving IFN-γR(-/-) T cells versus wild-type donor T cells displayed similar graft-versus-tumor (GVT) effects. These results demonstrate the critical role of IFN-γ on host tissues and cell effector functions in GVHD/GVT.

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عنوان ژورنال:
  • Journal of immunology

دوره 189 4  شماره 

صفحات  -

تاریخ انتشار 2012