title: CD8low CD100- T Cells Identify a Novel CD8 T Cell Subset Associated with Viral Control during Human Hantaan Virus Infection.
abstract: Hantaan virus (HTNV) infection can cause a severe lethal hemorrhagic fever with renal syndrome (HFRS) in humans. CD8(+) T cells play a critical role in combating HTNV infections. However, the contributions of different CD8(+) T cell subsets to the immune response against viral infection are poorly understood. Here, we identified a novel subset of CD8(+) T cells characterized by the CD8(low) CD100(-) phenotype in HFRS patients. The CD8(low) CD100(-) subset accounted for a median of 14.3% of the total CD8(+) T cells in early phase of HFRS, and this percentage subsequently declined in the late phase of infection, whereas this subset was absent in healthy controls. Furthermore, the CD8(low) CD100(-) cells were associated with high activation and expressed high levels of cytolytic effector molecules and exhibited a distinct expression profile of effector CD8(+) T cells (CCR7(+/-) CD45RA(-) CD127(high) CD27(int) CD28(low) CD62L(-)). When stimulated with specific HTNV nucleocapsid protein-derived peptide pools, most responding CD8(+) cells (gamma interferon [IFN-γ] positive and/or tumor necrosis factor alpha [TNF-α] positive) were CD8(low) CD100(-) cells. The frequency of CD8(low) CD100(-) cells among HTNV-specific CD8(+) T cells was higher in milder cases than in more severe cases. Importantly, the proportion of the CD8(low) CD100(-) subset among CD8(+) T cells in early phase of HFRS was negatively correlated with the HTNV viral load, suggesting that CD8(low) CD100(-) cells may be associated with viral clearance. The contraction of the CD8(low) CD100(-) subset in late phase of infection may be related to the consistently high expression levels of PD-1. These results may provide new insights into our understanding of CD8(+) T cell-mediated protective immunity as well as immune homeostasis after HTNV infection in humans.
  
  
  OBJECTIVE
  CD8(+) T cells play important roles in the antiviral immune response. We found that the proportion of CD8(low) CD100(-) cells among CD8(+) T cells from HFRS patients was negatively correlated with the HTNV viral load, and the frequency of CD8(low) CD100(-) cells among virus-specific CD8(+) T cells was higher in milder HFRS cases than in more severe cases. These results imply a beneficial role for the CD8(low) CD100(-) cell subset in viral control during human HTNV infection.
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Blood Transfusion, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Department of Infectious Disease, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China.
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China immuzy@fmmu.edu.cn immu_jin@fmmu.edu.cn.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, The Fourth Military Medical University, Xi'an, China immuzy@fmmu.edu.cn immu_jin@fmmu.edu.cn.
authors.forename: Boquan
authors.initials: B
authors.lastname: Jin
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002681:China; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005786:Gene Expression Regulation / Q000276:immunology*; D018063:Hantaan virus / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D039961:Semaphorins / Q000172:deficiency / Q000276:immunology*; D018709:Statistics, Nonparametric; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C093224:CD100 antigen; D039961:Semaphorins; D016650:Fluorescein-5-isothiocyanate