1. Acute HIV-1 infection is associated with increased plasma levels of heme oxygenase-1 and presence of heme oxygenase-1-specific regulatory T cells.
- Author
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Angin M, Fathi A, King M, Ledoux MB, Piechocka-Trocha A, Altfeld M, and Addo MM
- Subjects
- CD8-Positive T-Lymphocytes immunology, Cells, Cultured, Flow Cytometry, HIV Infections virology, Humans, Immunophenotyping, Longitudinal Studies, HIV Infections immunology, HIV-1 immunology, Heme Oxygenase-1 blood, Plasma enzymology, T-Lymphocytes, Regulatory immunology
- Abstract
Objective: Heme oxygenase-1 (HO-1) is an inducible stress response protein with potent anti-inflammatory activity and recent data suggest a potentially beneficial role in HIV pathogenesis. We investigated the impact of HO-1 and a novel subset of HO-1-specific CD8 regulatory T cells on virus-specific T-cell immunity in HIV-1-infected individuals., Methods: HO-1 protein levels were quantified in plasma from individuals at different stages of HIV-1 disease and longitudinally following primary HIV infection. HO-1-specific CD8 T cells were investigated by flow cytometry using human leukocyte antigen (HLA) class I pentamers. Flow-sorted HO-1-specific CD8 T cells were cultured and tested for suppressive activity on HIV-1-specific cytotoxic T-cell clones clones. HO-1 gene expression was determined in sorted peripheral blood mononuclear cell (PBMC) subsets from individuals with acute HIV-1 infection., Results: HO-1 plasma levels were significantly increased in HIV-1 infection, with the highest levels in individuals with acute HIV-1 infection, and gradually declined over time. The frequency of CD8 T cells specific for HO-1 was elevated in study participants with primary HIV-1 infection and flow-sorted HO-1-specific CD8 T cells were capable of suppressing HIV-1-specific lysis of cytotoxic T-cell clones clones. HO-1 gene expression was upregulated in multiple immune cell subsets during acute HIV-1 infection and HO-1 overexpression modulated anti-HIV immunity in vitro., Conclusion: Our data suggest that HO-1 is induced during acute HIV-1 infection, likely mediating anti-inflammatory effects and driving expansion of HO-1-specific CD8 regulatory T cells capable of suppressing HIV-1-specific immune responses in vitro. The investigation of HO-1 and the novel CD8 regulatory cell type described here provide further insight into immune regulation in HIV-1 infection and may hold potential for future immunotherapeutic intervention.
- Published
- 2017
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