Dynamics of CD4 and CD8 T-cell Subsets and Inflammatory Biomarkers during Early and Chronic HIV Infection in Mozambican Adults

作者：Pastor, Lucia^*; Urrea, Victor; Carrillo, Jorge; Parker, Erica; Fuente-Soro, Laura; Jairoce, Chenjerai; Mandomando, Inacio; Naniche, Denise; Blanco, Julia^*

来源：Frontiers in Immunology, 2018, 8: 1925.

DOI：10.3389/fimmu.2017.01925

• AIDS
• HIV pathogenesis
• T-cell exhaustion
• T-cell activation
• immunosenescence
• cytokines
• acute HIV infection
• sub-Saharan Africa

During primary HIV infection (PHI), 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 Manhica 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.

• 出版日期2018-1-5