title: Suppression of cytomegalovirus-specific CD8(+)T cells by everolimus.
abstract: 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.
authors.affiliation: Cellular Immunotherapy, Department of Internal Medicine V, Medical Clinic, University Clinic Heidelberg , Heidelberg , Germany.
authors.forename: Nan
authors.initials: N
authors.lastname: Jin
authors.forename: Georg
authors.initials: G
authors.lastname: Malcherek
authors.forename: Jiju
authors.initials: J
authors.lastname: Mani
authors.forename: Romy
authors.initials: R
authors.lastname: Zurleit
authors.forename: Anita
authors.initials: A
authors.lastname: Schmitt
authors.forename: Baoan
authors.initials: B
authors.lastname: Chen
authors.forename: Mathias
authors.initials: M
authors.lastname: Freund
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D037182:T-Cell Antigen Receptor Specificity / Q000187:drug effects* / Q000276:immunology*; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D010750:Phosphoproteins; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma; D000068338:Everolimus; D020123:Sirolimus