title: Early impairment of CD8+ T cells immune response against Epstein-Barr virus (EBV) antigens associated with high level of circulating mononuclear EBV DNA load in HIV infection.
abstract: Immunodeficiency related to HIV may increase the incidence of EBV-associated lymphomas, by altering EBV-specific immune control and consequently favoring EBV reactivation. The aim of the present study was to assess the relationship between the decrease of EBV-specific cellular immunity and the increase of EBV reactivation in a prospective cohort of 72 unselected HIV-infected individuals. EBV-specific immunity was evaluated by a highly sensitive IFN-gamma ELISPOT assay using 22 peptides mimicking latent and lytic antigens, and circulating mononuclear (PBMC) EBV DNA load was quantified by real-time quantitative PCR. The mean circulating cell-associated EBV DNA load was higher in HIV-infected patients (639 copies/10(6) PBMC) than in healthy controls (21, n = 14) ( P = 0.005) and was higher in patients with CD4(+) T-cell count below 350/microL than that in patients harboring higher CD4(+) T-cell count (1112 vs. 389, P = 0.003). The mean intensity of EBV-specific cellular responses was lower in HIV-infected patients than in controls ( P = 0.001), even in patients with CD4(+) T-cell count above 350/-microL ( P = 0.007). The number of EBV peptides recognized was lower in HIV-infected patients than in controls (frequency: 0.44 vs. 0.67; P = 0.02), indicating reduced polyclonality in HIV-infected patients. The polyclonality was 1.5-fold lower in HIV-infected patients with CD4(+) T-cell count below 350/-microL ( P =0.007). For EBV load >1000 copies/10(6) PBMC, the levels of cell-associated EBV DNA and those of EBV-specific cellular immunity, either in intensity or in polyclonality, or both, were inversely correlated. These findings demonstrate early impairment of the EBV-specific cellular immune control with progressive increase of EBV reactivation in the course of HIV infection. These observations likely provide a basis for appreciating the risk to develop non-Hodgkin's lymphomas in HIV-infected individuals.
authors.affiliation: Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris. jerome.legoff@hop.egp.ap-hop-paris.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Legoff
authors.forename: Corinne
authors.initials: C
authors.lastname: Amiel
authors.forename: Olivier
authors.initials: O
authors.lastname: Calisonni
authors.forename: Delphine
authors.initials: D
authors.lastname: Fromentin
authors.forename: Bakoliarisoa
authors.initials: B
authors.lastname: Rajoely
authors.forename: Nisen
authors.initials: N
authors.lastname: Abuaf
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.forename: Willy
authors.initials: W
authors.lastname: Rozenbaum
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Nicolas
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000032:analysis / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000276:immunology; D005602:France; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D010452:Peptide Biosynthesis; D020539:Sequence Analysis, Protein; D019562:Viral Load
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; D007371:Interferon-gamma