title: Early Gag immunodominance of the HIV-specific T-cell response during acute/early infection is associated with higher CD8+ T-cell antiviral activity and correlates with preservation of the CD4+ T-cell compartment.
abstract: The important role of the CD8(+) T-cell response on HIV control is well established. Moreover, the acute phase of infection represents a proper scenario to delineate the antiviral cellular functions that best correlate with control. Here, multiple functional aspects (specificity, ex vivo viral inhibitory activity [VIA] and polyfunctionality) of the HIV-specific CD8(+) T-cell subset arising early after infection, and their association with disease progression markers, were examined. Blood samples from 44 subjects recruited within 6 months from infection (primary HIV infection [PHI] group), 16 chronically infected subjects, 11 elite controllers (EC), and 10 healthy donors were obtained. Results indicated that, although Nef dominated the anti-HIV response during acute/early infection, a higher proportion of early anti-Gag T cells correlated with delayed progression. Polyfunctional HIV-specific CD8(+) T cells were detected at early time points but did not associate with virus control. Conversely, higher CD4(+) T-cell set points were observed in PHI subjects with higher HIV-specific CD8(+) T-cell VIA at baseline. Importantly, VIA levels correlated with the magnitude of the anti-Gag cellular response. The advantage of Gag-specific cells may result from their enhanced ability to mediate lysis of infected cells (evidenced by a higher capacity to degranulate and to mediate VIA) and to simultaneously produce IFN-γ. Finally, Gag immunodominance was associated with elevated plasma levels of interleukin 2 (IL-2) and macrophage inflammatory protein 1β (MIP-1β). All together, this study underscores the importance of CD8(+) T-cell specificity in the improved control of disease progression, which was related to the capacity of Gag-specific cells to mediate both lytic and nonlytic antiviral mechanisms at early time points postinfection.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. gturk@fmed.uba.ar
authors.forename: Gabriela
authors.initials: G
authors.lastname: Turk
authors.forename: Yanina
authors.initials: Y
authors.lastname: Ghiglione
authors.forename: Juliana
authors.initials: J
authors.lastname: Falivene
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Socias
authors.forename: Natalia
authors.initials: N
authors.lastname: Laufer
authors.forename: Romina Soledad
authors.initials: RS
authors.lastname: Coloccini
authors.forename: Ana María
authors.initials: AM
authors.lastname: Rodriguez
authors.forename: María Julia
authors.initials: MJ
authors.lastname: Ruiz
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Pando
authors.forename: Luis David
authors.initials: LD
authors.lastname: Giavedoni
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomon
authors.forename: María Magdalena
authors.initials: MM
authors.lastname: Gherardi
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology*; D001118:Argentina; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D015658:HIV Infections / Q000276:immunology*; D006680:HLA Antigens; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006680:HLA Antigens; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus