Hsp90 inhibition ameliorates CD4+ T cell-mediated acute Graft versus Host disease in mice

Immun Inflamm Dis. 2016 Oct 10;4(4):463-473. doi: 10.1002/iid3.127. eCollection 2016 Dec.


Introduction: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co-transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)-a potentially life-threatening complication.

Methods: Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD.

Results: Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4+ T cell transplantation with the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia-bearing mice after transplantation of allogeneic CD4+ and CD8+ T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4+ T cells with a relative resistance of CD4+ regulatory and CD8+ T cells toward Hsp90 inhibition.

Conclusions: Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.

Keywords: Acute graft‐versus‐host disease; CD4+ T cells; graft versus tumor; heat shock protein 90; hematopoietic stem cell transplantation; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Transplantation
  • CD4-Positive T-Lymphocytes*
  • Graft vs Host Disease / immunology*
  • HSP90 Heat-Shock Proteins / physiology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL


  • HSP90 Heat-Shock Proteins