Suppression of cytomegalovirus-specific CD8⁺T cells by everolimus

Abstract

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.

Keywords::

• Everolimus
• immunosuppression
• cytomegalovirus
• mixed lymphocyte peptide culture
• pp65-specific CD8 ⁺ T cells

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