Link to Pubmed [PMID] – 28060008
AIDS 2017 Jan;
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 here 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 HLA-class-I-pentamers. Flow-sorted HO-1-specific CD8 T cells were cultured and tested for suppressive activity on HIV-1-specific CTL clones. HO-1 gene expression was determined in sorted PBMC subsets from individuals with acute HIV-1 infection.
RESULTS: HO-1 plasma levels were significantly increased in HIV-1 infection with 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 subjects with primary HIV-1 infection and flow-sorted HO-1-specific CD8 T cells were capable of suppressing HIV-1-specific lysis of CTL 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 Tregs 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.