科研之友
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摘要
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.
- 出版日期2017-3-13
- 单位MIT
