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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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
Externally publishedYes

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Antiviral Agents
T-lymphocytes
HIV
T-Lymphocytes
Infection
infection
HIV Infections
Disease Progression
HIV infections
T-Cell Antigen Receptor Specificity
disease course
Macrophage Inflammatory Proteins
T-Lymphocyte Subsets
Interleukin-2
cells
interleukin-2
Viruses
viruses
blood
sampling

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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

In: Journal of Virology, Vol. 87, No. 13, 07.2013, p. 7445-7462.

Research output: Contribution to journalArticle

Turk, G, Ghiglione, Y, Falivene, J, Socias, ME, Laufer, N, Coloccini, RS, Rodriguez, AM, Ruiz, MJ, Pando, MÁ, Giavedoni, LD, Cahn, P, Sued, O, Salomon, H & Gherardi, MM 2013, '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', Journal of Virology, vol. 87, no. 13, pp. 7445-7462. https://doi.org/10.1128/JVI.00865-13
Turk, Gabriela ; Ghiglione, Yanina ; Falivene, Juliana ; Socias, María Eugenia ; Laufer, Natalia ; Coloccini, Romina Soledad ; Rodriguez, Ana María ; Ruiz, María Julia ; Pando, María Ángeles ; Giavedoni, Luis David ; Cahn, Pedro ; Sued, Omar ; Salomon, Horacio ; Gherardi, María Magdalena. / 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. In: Journal of Virology. 2013 ; Vol. 87, No. 13. pp. 7445-7462.
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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.",
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AU - Falivene, Juliana

AU - Socias, María Eugenia

AU - Laufer, Natalia

AU - Coloccini, Romina Soledad

AU - Rodriguez, Ana María

AU - Ruiz, María Julia

AU - Pando, María Ángeles

AU - Giavedoni, Luis David

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AU - Sued, Omar

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