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.…
Author: | Carsten Berges, Thomas Kerkau, Sandra Werner, Nelli Wolf, Nadine Winter, Thomas Hünig, Hermann Einsele, Max S. Topp, Niklas Beyersdorf |
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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): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |