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+ TCell compartment

Gabriela Turk, Yanina Ghiglione, Juliana Falivene, María Eugenia Socias, Natalia Laufer, Romina Soledad Coloccini, Ana María Rodriguez, María Julia Ruiz, María Ángeles Pando, Luis David Giavedoni, Pedro Cahn, Omar Sued, Horacio Salomon, María Magdalena Gherardi

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    33 Scopus citations

    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.

    Original languageEnglish (US)
    Pages (from-to)7445-7462
    Number of pages18
    JournalJournal of virology
    Volume87
    Issue number13
    DOIs
    StatePublished - Jul 2013

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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