Dynamics of CD4 and CD8 T-cell subsets and inflammatory biomarkers during early and chronic HIV infection in Mozambican adults

Lucía Pastor, Victor Urrea, Jorge Carrillo, Erica Parker, Laura Fuente-Soro, Chenjerai Jairoce, Inacio Mandomando, Denise Naniche, Julià Blanco

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    Abstract

    During primary HIV infection, there is a striking cascade response of inflammatory cytokines and many cells of the immune system show altered frequencies and signs of extensive activation. These changes have been shown to have a relevant role in predicting disease progression; however, the challenges of identifying PHI have resulted in a lack of critical information about the dynamics of early pathogenic events. We studied soluble inflammatory biomarkers and changes in T-cell subsets in individuals at PHI (n = 40), chronic HIV infection (CHI, n = 56), and HIV-uninfected (n = 58) recruited at the Manhiça District Hospital in Mozambique. Plasma levels of 49 biomarkers were determined by Luminex and ELISA. T-cell immunophenotyping was performed by multicolor flow cytometry. Plasma HIV viremia, CD4, and CD8 T cell counts underwent rapid stabilization after PHI. However, several immunological parameters, including Th1-Th17 CD4 T cells and activation or exhaustion of CD8 T cells continued decreasing until more than 9 months postinfection. Importantly, no sign of immunosenescence was observed over the first year of HIV infection. Levels of IP-10, MCP-1, BAFF, sCD14, tumor necrosis factor receptor-2, and TRAIL were significantly overexpressed at the first month of infection and underwent a prompt decrease in the subsequent months while, MIG and CD27 levels began to increase 1 month after infection and remained overexpressed for almost 1 year postinfection. Early levels of soluble biomarkers were significantly associated with subsequently exhausted CD4 T-cells or with CD8 T-cell activation. Despite rapid immune control of virus replication, the stabilization of the T-cell subsets occurs months after viremia and CD4 count plateau, suggesting persistent immune dysfunction and highlighting the potential benefit of early treatment initiation that could limit immunological damage.

    Original languageEnglish
    Article number1925
    JournalFrontiers in Immunology
    Volume8
    Issue numberJAN
    DOIs
    Publication statusPublished - 5 Jan 2018

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    Pastor, L., Urrea, V., Carrillo, J., Parker, E., Fuente-Soro, L., Jairoce, C., Mandomando, I., Naniche, D., & Blanco, J. (2018). Dynamics of CD4 and CD8 T-cell subsets and inflammatory biomarkers during early and chronic HIV infection in Mozambican adults. Frontiers in Immunology, 8(JAN), [1925]. https://doi.org/10.3389/fimmu.2017.01925