Suppression of cytomegalovirus-specific CD8+T cells by everolimus. Issue 5 (May 2014)

• Record Type: Journal Article
• Authors: Jin, Nan; Malcherek, Georg; Mani, Jiju; Zurleit, Romy; Schmitt, Anita; Chen, Baoan; Freund, Mathias; Ho, Anthony D.; Schmitt, Michael
• Is Part Of: Leukemia & lymphoma. Volume 55:Issue 5(2014:May)
• Page Start: 1144
• Page End: 1150
• Publication Date: 2014-05
• Subjects: Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2013.822496
• Languages: English
• ISSNs: 1042-8194

Abstract

<abstract> <title>Abstract</title> <p>Everolimus (RAD-001) has recently been used as an immunosuppressive drug to treat patients after hematopoietic stem cell transplant (HSCT), thereby reducing cyclosporine-related nephrotoxicity. We studied the immunomodulatory effect of everolimus on mitogen-stimulated and particularly cytomegalovirus (CMV)-specific cytotoxic T cells. Proliferation of CD4⁺ and CD8⁺ T cells stimulated with staphylococcal endotoxin B and phytohemagglutinin was strongly inhibited at very low doses. Proliferation of CMV-specific CD8⁺ T cells could be completely suppressed. Similarly, the frequency of CMV-specific, cytokine-secreting and CD137-expressing CD8⁺ T cells decreased in a dose-dependent manner. However, interferon-γ (IFN-γ) secretion by CMV-specific CD8⁺ T cells remained unchanged, as could be demonstrated by intracellular cytokine staining. As reactivation of CMV plays a pivotal role in the outcome of patients after HSCT, attention must be paid to early detection and preemptive treatment of CMV reactivity in patients treated with everolimus.</p> </abstract>