CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection

Marcus Buggert, Juliet Wairimu Frederiksen, Ole Lund, Michael R. Betts, Antonio Biague, Morten Nielsen, Johanna Tauriainen, Hans Norrgren, Patrik Medstrand, Annika C. Karlsson, Marianne Jansson

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    Abstract

    OBJECTIVE: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. DESIGN: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2-infected subjects had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with suboptimal percentage of CD4+ T cells. CONCLUSIONS: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of ART also to individuals with aviremic HIV-2 infection.
    Original languageEnglish
    JournalAIDS
    Volume30
    Issue number16
    Pages (from-to)2415-2426
    ISSN0269-9370
    DOIs
    Publication statusPublished - 2016

    Bibliographical note

    This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

    Keywords

    • Activation
    • CD4+ T cells
    • Exhaustion
    • HIV-1
    • HIV-2
    • Immunodeficiency
    • Viremia

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