PMID- 28060008 OWN - NLM STAT- MEDLINE DCOM- 20180102 LR - 20181027 IS - 1473-5571 (Electronic) IS - 0269-9370 (Linking) VI - 31 IP - 5 DP - 2017 Mar 13 TI - Acute HIV-1 infection is associated with increased plasma levels of heme oxygenase-1 and presence of heme oxygenase-1-specific regulatory T cells. PG - 635-641 LID - 10.1097/QAD.0000000000001390 [doi] AB - 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. FAU - Angin, Mathieu AU - Angin M AD - aRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA bUniversity of Munster, Munster, North Rhine-Westphalia cDepartment of Viral Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany dDivision of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA eI. Department of Medicine, University Medical Center Hamburg-Eppendorf fGerman Center for Infection Research (DZIF), Standort Hamburg-Luebeck-Borstel, Hamburg, Germany. FAU - Fathi, Anahita AU - Fathi A FAU - King, Melanie AU - King M FAU - Ledoux, Mary B AU - Ledoux MB FAU - Piechocka-Trocha, Alicja AU - Piechocka-Trocha A FAU - Altfeld, Marcus AU - Altfeld M FAU - Addo, Marylyn M AU - Addo MM LA - eng PT - Journal Article PL - England TA - AIDS JT - AIDS (London, England) JID - 8710219 RN - EC 1.14.14.18 (Heme Oxygenase-1) SB - IM MH - CD8-Positive T-Lymphocytes/immunology MH - Cells, Cultured MH - Flow Cytometry MH - HIV Infections/*immunology/virology MH - HIV-1/*immunology MH - Heme Oxygenase-1/*blood MH - Humans MH - Immunophenotyping MH - Longitudinal Studies MH - Plasma/*enzymology MH - T-Lymphocytes, Regulatory/*immunology EDAT- 2017/01/07 06:00 MHDA- 2018/01/03 06:00 CRDT- 2017/01/07 06:00 PHST- 2017/01/07 06:00 [pubmed] PHST- 2018/01/03 06:00 [medline] PHST- 2017/01/07 06:00 [entrez] AID - 10.1097/QAD.0000000000001390 [doi] PST - ppublish SO - AIDS. 2017 Mar 13;31(5):635-641. doi: 10.1097/QAD.0000000000001390.