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Hsp90 inhibition ameliorates CD4+T cell-mediated acute Graft versus Host disease in mice
| Content Provider | Scilit |
|---|---|
| Author | Berges, Carsten Kerkau, Thomas Werner, Sandra Wolf, Nelli Winter, Nadine Hünig, Thomas Einsele, Hermann Topp, Max S. Beyersdorf, Niklas |
| Copyright Year | 2016 |
| Description | Journal: Immunity, Inflammation and Disease 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. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5134726/pdf |
| Ending Page | 473 |
| Page Count | 11 |
| Starting Page | 463 |
| e-ISSN | 20504527 |
| DOI | 10.1002/iid3.127 |
| Journal | Immunity, Inflammation and Disease |
| Issue Number | 4 |
| Volume Number | 4 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2016-10-10 |
| Access Restriction | Open |
| Subject Keyword | Journal: Immunity, Inflammation and Disease Research and Experimental Medicine Acute Graft‐versus‐host Disease Cd4+ T Cells Graft Versus Tumor Heat Shock Protein 90 Hematopoietic Stem Cell Transplantation Regulatory T Cells |
| Content Type | Text |
| Resource Type | Article |
