Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice

Please always quote using this URN: urn:nbn:de:bvb:20-opus-168318
  • 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 whetherIntroduction: 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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Carsten Berges, Thomas Kerkau, Sandra Werner, Nelli Wolf, Nadine Winter, Thomas Hünig, Hermann Einsele, Max S. Topp, Niklas Beyersdorf
URN:urn:nbn:de:bvb:20-opus-168318
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Virologie und Immunbiologie
Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Immunity, Inflammation and Disease
Year of Completion:2016
Volume:4
Issue:4
Pagenumber:463-473
Source:Immunity, Inflammation and Disease 2016, 4(4): 463-473. DOI: 10.1002/iid3.127
DOI:https://doi.org/10.1002/iid3.127
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Graft versus Tumor; Hsp90; acute Graft versus Host Disease; leukemia
Release Date:2019/09/02
Collections:Open-Access-Publikationsfonds / Förderzeitraum 2016
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International