title: Development of virus-specific CD4+ and CD8+ regulatory T cells induced by human herpesvirus 6 infection.
abstract: Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus. The mechanisms by which HHV-6 establishes latency and immunosuppression in its host are not well understood. Here we characterized HHV-6-specific T cells in peripheral blood mononuclear cells (PBMCs) from HHV-6-infected donors. Our results showed that HHV-6 infection could induce both CD4(+) and CD8(+) HHV-6-specific regulatory T (Treg) cells. These HHV-6-specific Treg cells had potent suppressive activity and expressed high levels of Treg-associated molecules CD25, FoxP3, and GITR. Both CD4(+) and CD8(+) Treg cells secreted gamma interferon (IFN-γ) and interleukin-10 (IL-10) but little or no IL-2, IL-4, or transforming growth factor β (TGF-β). Furthermore, HHV-6-specifc Treg cells not only could suppress naive and HHV-6-specific CD4(+) effector T cell immune responses but also could impair dendritic cell (DC) maturation and functions. In addition, the suppressive effects mediated by HHV-6-specific Treg cells were mainly through a cell-to-cell contact-dependent mechanism but not through the identified cytokines. These results suggest that HHV-6 may utilize the induction of Treg cells as a strategy to escape antivirus immune responses and maintain the latency and immunosuppression in infected hosts.
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Chi
authors.forename: Guangyong
authors.initials: G
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Zhou
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.forename: Lingyun
authors.initials: L
authors.lastname: Li
authors.forename: Dongju
authors.initials: D
authors.lastname: Feng
authors.forename: Fangyi
authors.initials: F
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Gu
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Yao
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D019349:Roseolovirus Infections / Q000276:immunology* / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology
chemical_list: D007371:Interferon-gamma