title: Cytokine and cellular responses to human herpesvirus-6B in patients with B-acute lymphoblastic leukemia.
abstract: Primary infection with human herpesvirus-6 (HHV-6), is followed by its lifelong persistence in the host. Most T-cell responses to HHV-6 have been characterized using peripheral blood from healthy adults; however, the role of HHV-6 infection in immune modulation has not been elucidated for some diseases. Therefore, in this study the immune response to HHV-6 infection in patients with B-acute lymphoblastic leukemia (B-ALL) was analyzed. HHV-6 load was quantified in blood samples taken at the time of diagnosis of leukemia and on remission. The same concentrations of anti- and pro-inflammatory cytokines (IL-4, IL-1, IL-6, IL-8, IL-12p70, IL-17a, TNF-α and IFN-γ) were detected in plasma samples from 20 patients with and 20 without detectable HHV-6 virus loads in blood. Characterization of T-cell responses to HHV-6 showed low specific T-cells frequencies of 2.08% and 1.46% in patients with and without detectable viral loads, respectively. IFN-γ-producing T cells were detected in 0.03%-0.23% and in 0%-0.2% of CD4+T cells, respectively. Strong production of IL-6 was detected in medium supernatants of challenged T-cells whatever the HHV-6 status of the patients (973.51 ± 210.06 versus 825.70 ± 210.81 pg/mL). However, concentrations of TNF-α and IFN-γ were low. Thus, no association between plasma concentrations of cytokines and detection of HHV-6 in blood was identified, suggesting that HHV-6 is not strongly associated with development of B-ALL. The low viral loads detected may correspond with latently infected cells. Alternatively, HHV-6B specific immune responses may be below the detection threshold of the assays used.
authors.affiliation: Laboratory of Transmissible Diseases and Biological Active Substances, LR99ES27, Faculty of Pharmacy, University of Monastir, Street Avicenne 5000, Monastir, Tunisia.
authors.forename: Faten
authors.initials: F
authors.lastname: Nefzi
authors.affiliation: Immunology Laboratory, Georges Friedel Laboratory (CNRS UMR5307); University Hospital of Saint-Étienne, 44 Rue Pointe Cadet, 42100 Saint-Étienne, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Lambert
authors.affiliation: Sorbonne University, Pierre and Marie Curie University, Center for Immunology and Infectious Diseases of Paris (UMRS CR7), Persistent Viral Infections Team, 4 Jussieu Place, 75005, Paris, France.|Public Assistance-Hospitals of Paris, University Hospitals Pitié Salpêtrière-Charles Foix, Virology Service, 3 Avenue Victoria, 75004 Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Gautheret-Dejean
authors.affiliation: INSERM U951, University of Evry Val d'Essonne, UMR_S951, Genethon, F-91002 Evry, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fisson
authors.affiliation: INSERM U951, University of Evry Val d'Essonne, UMR_S951, Genethon, F-91002 Evry, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Khebizi
authors.affiliation: Department of Clinical Hematology, Farhat Hached Hospital, Sousse, Tunisia.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Khelif
authors.affiliation: Sorbonne University, Pierre and Marie Curie University, Center for Immunology and Infectious Diseases of Paris (UMRS CR7), Persistent Viral Infections Team, 4 Jussieu Place, 75005, Paris, France.|Public Assistance-Hospitals of Paris, University Hospitals Pitié Salpêtrière-Charles Foix, Virology Service, 3 Avenue Victoria, 75004 Paris, France.
authors.forename: Henri
authors.initials: H
authors.lastname: Agut
authors.affiliation: Laboratory of Transmissible Diseases and Biological Active Substances, LR99ES27, Faculty of Pharmacy, University of Monastir, Street Avicenne 5000, Monastir, Tunisia.
authors.forename: Mahjoub
authors.initials: M
authors.lastname: Aouni
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D004279:DNA, Viral; D005077:Exanthema Subitum / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005260:Female; D015654:Herpesvirus 6, Human / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019562:Viral Load; D055815:Young Adult
chemical_list: D016207:Cytokines; D004279:DNA, Viral
keywords: B-acute lymphoblastic leukemia; T cell responses; cytokines; human herpesvirus-6