Early skewed distribution of total and HIV-specific CD8+ T-cell memory phenotypes during primary HIV infection is related to reduced antiviral activity and faster disease progression

Yanina Ghiglione, Juliana Falivene, María Julia Ruiz, Natalia Laufer, María Eugenia Socías, Pedro Cahn, Luis Giavedoni, Omar Sued, María Magdalena Gherardi, Horacio Salomón, Gabriela Turk

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    20 Scopus citations

    Abstract

    The important role of the CD8+ T-cells on HIV control is well established. However, correlates of immune protection remain elusive. Although the importance of CD8+ T-cell specificity and functionality in virus control has been underscored, further unraveling the link between CD8 + T-cell differentiation and viral control is needed. Here, an immunophenotypic analysis (in terms of memory markers and Programmed cell death 1 (PD-1) expression) of the CD8+ T-cell subset found in primary HIV infection (PHI) was performed. The aim was to seek for associations with functional properties of the CD8+ T-cell subsets, viral control and subsequent disease progression. Also, results were compared with samples from Chronics and Elite Controllers. It was found that normal maturation of total and HIV-specific CD8+ T-cells into memory subsets is skewed in PHI, but not at the dramatic level observed in Chronics. Within the HIV-specific compartment, this alteration was evidenced by an accumulation of effector memory CD8+ T (TEM) cells over fully differentiated terminal effector CD8+ T (TTE) cells. Furthermore, higher proportions of total and HIV-specific CD8+ TEM cells and higher HIV-specific TEM/(TEM+TTE) ratio correlated with markers of faster progression. Analysis of PD-1 expression on total and HIV-specific CD8+ T-cells from PHI subjects revealed not only an association with disease progression but also with skewed memory CD8+ T-cell differentiation. Most notably, significant direct correlations were obtained between the functional capacity of CD8+ T-cells to inhibit viral replication in vitro with higher proportions of fully-differentiated HIV-specific CD8+ TTE cells, both at baseline and at 12 months post-infection. Thus, a relationship between preservation of CD8+ T-cell differentiation pathway and cell functionality was established. This report presents evidence concerning the link among CD8+ T-cell function, phenotype and virus control, hence supporting the instauration of early interventions to prevent irreversible immune damage.

    Original languageEnglish (US)
    Article numbere104235
    JournalPloS one
    Volume9
    Issue number8
    DOIs
    StatePublished - Aug 5 2014

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

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    Ghiglione, Y., Falivene, J., Ruiz, M. J., Laufer, N., Socías, M. E., Cahn, P., Giavedoni, L., Sued, O., Gherardi, M. M., Salomón, H., & Turk, G. (2014). Early skewed distribution of total and HIV-specific CD8+ T-cell memory phenotypes during primary HIV infection is related to reduced antiviral activity and faster disease progression. PloS one, 9(8), [e104235]. https://doi.org/10.1371/journal.pone.0104235