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.
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.
Legoff
Jérôme
J
Laboratoire de Virologie, Hôpital Européen Georges Pompidou, Paris. jerome.legoff@hop.egp.ap-hop-paris.fr
Amiel
Corinne
C
Calisonni
Olivier
O
Fromentin
Delphine
D
Rajoely
Bakoliarisoa
B
Abuaf
Nisen
N
Tartour
Eric
E
Rozenbaum
Willy
W
Bélec
Laurent
L
Nicolas
Jean-Claude
JC
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
D000956:Antigens, Viral; D004279:DNA, Viral; D007371:Interferon-gamma