title: Association of lymph-node antigens with lower Gag-specific central-memory and higher Env-specific effector-memory CD8(+) T-cell frequencies in a macaque AIDS model.
abstract: Virus-specific CD8(+) T cells exert strong suppressive pressure on human/simian immunodeficiency virus (HIV/SIV) replication. These responses have been intensively examined in peripheral blood mononuclear cells (PBMCs) but not fully analyzed in lymph nodes (LNs), where interaction between CD8(+) T cells and HIV/SIV-infected cells occurs. Here, we investigated target antigen specificity of CD8(+) T cells in LNs in a macaque AIDS model. Analysis of virus antigen-specific CD8(+) T-cell responses in the inguinal LNs obtained from twenty rhesus macaques in the chronic phase of SIV infection showed an inverse correlation between viral loads and frequencies of CD8(+) T cells with CD28(+) CD95(+) central memory phenotype targeting the N-terminal half of SIV core antigen (Gag-N). In contrast, analysis of LNs but not PBMCs revealed a positive correlation between viral loads and frequencies of CD8(+) T cells with CD28(-)CD95(+) effector memory phenotype targeting the N-terminal half of SIV envelope (Env-N), soluble antigen. Indeed, LNs with detectable SIV capsid p27 antigen in the germinal center exhibited significantly lower Gag-N-specific CD28(+) CD95(+) CD8(+) T-cell and higher Env-N-specific CD28(-)CD95(+) CD8(+) T-cell responses than those without detectable p27. These results imply that core and envelope antigen-specific CD8(+) T cells show different patterns of interactions with HIV/SIV-infected cells.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuoka
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.|Center for AIDS Research, Kumamoto University, Tokyo 162-8640, Japan.
authors.forename: Takushi
authors.initials: T
authors.lastname: Nomura
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Teiichiro
authors.initials: T
authors.lastname: Shiino
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwata-Yoshikawa
authors.affiliation: Department of Pathology, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Kazuta
authors.initials: K
authors.lastname: Mizuta
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakawaki
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miura
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Koyanagi
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Taeko K
authors.initials: TK
authors.lastname: Naruse
authors.affiliation: Department of Molecular Pathogenesis, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.|The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008251:Macaca / Q000276:immunology*; D008253:Macaca mulatta / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D019562:Viral Load / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D015686:Gene Products, env