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Blood, 24 September 2009, Vol. 114, No. 13, pp. 2829-2836. Prepublished online as a Blood First Edition Paper on August 5, 2009; DOI 10.1182/blood-2009-06-224600. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-06-224600v1 114/13/2829    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Stuehler, C. Articles by Topp, M. S. PubMed PubMed Citation Articles by Stuehler, C. Articles by Topp, M. S. Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Selective depletion of alloreactive T cells by targeted therapy of heat shock protein 90: a novel strategy for control of graft-versus-host disease Claudia Stuehler1, Stephan Mielke*,1, Manik Chatterjee*,1, Johannes Duell1, Sarah Lurati1, Florian Rueckert1, Hermann Einsele1, Ralf C. Bargou1, and Max S. Topp1 1 Department of Internal Medicine II, Division of Hematology, University Hospital of Wuerzburg, Wuerzburg, Germany Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in patients with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation. Current treatment of GVHD relies on immunosuppressive regimens, considerably increasing the incidence of opportunistic infections. As T cells mediate both GVHD as well as protection against viral infections and the malignant disease, strategies to selectively target host-reactive T cells without impairing pathogen- and disease-specific immunity are highly warranted. Activation of T cells is accompanied by increased expression of the chaperone heat shock protein of 90 kDa (Hsp90), which stabilizes several key signaling pathways crucial for T-cell activation. In this study, selective targeting of Hsp90 in activated T lymphocytes with pharmacologic inhibitors already applied successfully in anticancer therapy resulted in induction of apoptosis predominantly in activated cells. Moreover, if T cells were stimulated with allogeneic dendritic cells, alloreactive T cells were selectively eliminated. In contrast, third party reactions including antiviral T-cell immunity were quantitatively and functionally fully preserved. These data suggest that Hsp90 represents a novel target for selective depletion of alloreactive T cells, and provide the rationale for application of Hsp90 inhibitors as potential approach to selectively prevent and treat GVHD in hematopoietic stem cell transplantation recipients without impairing pathogen- and disease-specific T-cell immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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