title: Inducible-costimulator-mediated suppression of human immunodeficiency virus type 1 replication in CD4(+) T lymphocytes.
abstract: We investigated the effects of signaling through CD28 family molecules on human immunodeficiency virus type 1 (HIV-1) replication in vitro. A monoclonal antibody (mAb) specific for inducible costimulator (ICOS) suppressed both X4 and R5 HIV-1 replication in CD4(+) peripheral blood mononuclear cells (PBMC). This suppression was not attributable to reduced cell growth or viability. CD28 mAb showed variable effects and also suppressed HIV-1 replication when immobilized. Replication of pseudotype viruses with HIV-1-but not with vesicular stomatitis virus G-envelope was efficiently suppressed in CD4(+) PBMC treated with ICOS or CD28 mAbs. However, CD4, CXCR4, and CCR5 expression on the surface was not down-regulated. Moreover, HIV-1 replication in CD4(+) PBMC was suppressed by a soluble form of human B7-H2, a ligand of ICOS, but was enhanced by soluble B7-1, a ligand for CD28. These findings suggest that natural or artificial ligands for ICOS potentially suppress HIV-1 replication mainly at the entry stages.
authors.affiliation: Department of Immunotherapeutics, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Makoto
authors.initials: M
authors.lastname: Kubo
authors.forename: Hironori
authors.initials: H
authors.lastname: Nishitsuji
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kurihara
authors.forename: Tamako
authors.initials: T
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohashi
authors.forename: Miyuki
authors.initials: M
authors.lastname: Azuma
authors.forename: Takao
authors.initials: T
authors.lastname: Masuda
authors.forename: Mari
authors.initials: M
authors.lastname: Kannagi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002455:Cell Division; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D060889:Inducible T-Cell Co-Stimulator Protein; D007555:Isoxazoles / Q000494:pharmacology; D000077339:Leflunomide; D008024:Ligands; D051379:Mice; D015728:Receptors, HIV / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D018106:CD28 Antigens; D016207:Cytokines; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D007555:Isoxazoles; D008024:Ligands; D015728:Receptors, HIV; D000077339:Leflunomide