title: Hsp90 inhibition ameliorates CD4+T cell-mediated acute Graft versus Host disease in mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.
authors.affiliation: Department of Internal Medicine II Division of Hematology University Hospital Würzburg Würzburg Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Berges
authors.affiliation: Institute for Virology and Immunobiology University of Würzburg Würzburg Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kerkau
authors.affiliation: Institute for Virology and Immunobiology University of Würzburg Würzburg Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Werner
authors.affiliation: Institute for Virology and Immunobiology University of Würzburg Würzburg Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Wolf
authors.affiliation: Department of Internal Medicine II Division of Hematology University Hospital Würzburg Würzburg Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Winter
authors.affiliation: Institute for Virology and Immunobiology University of Würzburg Würzburg Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.affiliation: Department of Internal Medicine II Division of Hematology University Hospital Würzburg Würzburg Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.affiliation: Department of Internal Medicine II Division of Hematology University Hospital Würzburg Würzburg Germany.
authors.forename: Max S
authors.initials: MS
authors.lastname: Topp
authors.affiliation: Institute for Virology and Immunobiology University of Würzburg Würzburg Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Beyersdorf
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes; D006086:Graft vs Host Disease / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D018841:HSP90 Heat-Shock Proteins
keywords: Acute graft‐versus‐host disease; CD4+ T cells; graft versus tumor; heat shock protein 90; hematopoietic stem cell transplantation; regulatory T cells