Dataset Information

Plasmatic Levels of IL-18, IP-10, and Activated CD8+ T Cells Are Potential Biomarkers to Identify HIV-1 Elite Controllers With a True Functional Cure Profile.

ABSTRACT: Elite controllers (ECs) are rare individuals able to naturally control HIV-1 replication below the detection limit of viral load (VL) commercial assays. It is unclear, however, whether ECs might be considered a natural model of a functional cure because some studies have noted CD4+ T cell depletion and disease progression associated with abnormally high levels of immune activation and/or inflammation in this group. Here, we propose the use of immunological parameters to identify HIV-1 ECs that could represent the best model of a functional cure. We compared plasma levels of six inflammatory biomarkers (IP-10, IL-18, sCD163, sCD14, CRP, and IL-6) and percentages of activated CD8+ T cells (CD38+HLA-DR+) between 15 ECs [8 with persistent undetectable viremia (persistent elite controllers) and 7 with occasional viral blips (ebbing elite controllers)], 13 viremic controllers (VCs-plasma VL between 51 and 2,000?RNA copies/mL), and 18 HIV-1 infected patients in combined antiretroviral therapy, with suppressed viremia, and 18 HIV-uninfected controls (HIV-neg). The two groups of ECs presented inflammation and activation profiles similar to HIV-neg individuals, and there was no evidence of CD4+ T cell decline over time. VCs, by contrast, had higher levels of IL-18, IP-10, and CRP and a lower CD4/CD8 ratio than that of HIV-neg (P?5?years, show no evidence of persistent inflammation or immune activation. This study further suggests that plasmatic levels of IL-18/IP-10 combined with the frequency of CD8+CD38+HLA-DR+ T cells can be important biomarkers to identify models of a functional cure among HIV-1 ECs.

SUBMITTER: Cortes FH

PROVIDER: S-EPMC6050358 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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Plasmatic Levels of IL-18, IP-10, and Activated CD8<sup>+</sup> T Cells Are Potential Biomarkers to Identify HIV-1 Elite Controllers With a True Functional Cure Profile.

Côrtes Fernanda H FH de Paula Hury H S HHS Bello Gonzalo G Ribeiro-Alves Marcelo M de Azevedo Suwellen S D SSD Caetano Diogo G DG Teixeira Sylvia L M SLM Hoagland Brenda B Grinsztejn Beatriz B Veloso Valdilea G VG Guimarães Monick L ML Morgado Mariza G MG

Frontiers in immunology 20180711

Elite controllers (ECs) are rare individuals able to naturally control HIV-1 replication below the detection limit of viral load (VL) commercial assays. It is unclear, however, whether ECs might be considered a natural model of a functional cure because some studies have noted CD4<sup>+</sup> T cell depletion and disease progression associated with abnormally high levels of immune activation and/or inflammation in this group. Here, we propose the use of immunological parameters to identify HIV-1 ...[more]

PMID: 30050532

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Project description:ObjectiveElite controllers, defined as persons maintaining undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, represent living evidence that sustained, natural control of HIV-1 is possible, at least in relatively rare instances. Understanding the complex immunologic and virologic characteristics of these specific patients holds promise for inducing drug-free control of HIV-1 in broader populations of HIV-1 infected patients.DesignWe used an unbiased transcriptional profiling approach to characterize CD8+ T cells, the strongest correlate of HIV-1 immune control identified thus far, in a large cohort of elite controllers (n = 51); highly active antiretrovial therapy (HAART)-treated patients (n = 32) and HIV-1 negative (n = 10) served as reference cohorts.MethodsWe isolated mRNA from total CD8+ T cells isolated from peripheral blood mononuclear cell (PBMC) of each individual followed by microarray analysis of the transcriptional signatures.ResultsWe observed profound transcriptional differences [590 transcripts, false discovery rate (FDR)-adjusted P < 0.05] between elite controller and HAART-treated patients. Interestingly, metabolic and signalling pathways governed by mammalian target of rapamycin (mTOR) and eIF2, known for their key roles in regulating cellular growth, proliferation and metabolism, were among the top functions enriched in the differentially expressed genes, suggesting a therapeutically actionable target as a distinguishing feature of spontaneous HIV-1 immune control. A subsequent bootstrapping approach distinguished five different subgroups of elite controller, each characterized by distinct transcriptional signatures. However, despite this marked heterogeneity, differential regulation of mTOR and eIF2 signalling remained the dominant functional pathway in three of these elite controller subgroups.ConclusionThese studies suggest that mTOR and eIF2 signalling may play a remarkably universal role for regulating CD8 T-cell function from elite controllers.

Dataset Information

Plasmatic Levels of IL-18, IP-10, and Activated CD8+ T Cells Are Potential Biomarkers to Identify HIV-1 Elite Controllers With a True Functional Cure Profile.

Publications

Plasmatic Levels of IL-18, IP-10, and Activated CD8<sup>+</sup> T Cells Are Potential Biomarkers to Identify HIV-1 Elite Controllers With a True Functional Cure Profile.

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