title: Induction of rapid apoptosis for class I MHC molecule-restricted CD8(+) HIV-1 gp160-specific murine activated CTLs by free antigenic peptide in vivo.
abstract: We have previously reported that the cytotoxic activity of murine CD8(+) CTLs specific for HIV-1 gp160 envelope protein was markedly inhibited in vitro by brief exposure to a free epitope peptide P18-I10 (aa: RGPGRAFVTI) using the epitope-specific CTL line (LINE-IIIB) or a clone (RT-1). We have also shown that recently stimulated P18-I10-specific murine CTLs rapidly fell into apoptosis in vitro after brief exposure to the free epitope peptide. In the present study, we examined whether similar inactivation or apoptosis of recently stimulated CTLs occurred in vivo by exposure to the free epitope peptide using TCR transgenic (Tg-RT-1) mice expressing TCRαβ genes of CTL clone RT-1. When the Tg mice were inoculated with recombinant vaccinia virus expressing HIV-1-IIIB gp160 genes followed by injection of P18-I10 epitope peptide, apparent reduction in the number of CTLs determined by flow cytometry using H-2D(d)/P18-I10 pentamer was observed within a few hours after the injection. Most of the H-2D(d)/P18-I10 pentamer-stained cells were positive for Annexin V and apoptosis was confirmed by microscopic analyses. Moreover, when mice were pretreated with immunosuppressive agents, such as cyclosporin A and tacrolimus (FK506), induction of apoptosis by P18-I10 was significantly inhibited and CTL cytotoxicity was maintained. These results suggest that the rapid loss of virus-specific CD8(+) CTLs might occur in vivo through apoptosis in the early stages of viral infection when activated CTLs may encounter viral epitope(s) released from virus-infected cells attacked by CTLs and we can prevent the loss by pretreatment with immunosuppressive agents.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Tokyo 113-8602, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Norose
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology; D016572:Cyclosporine / Q000008:administration & dosage; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D015488:HIV Antigens / Q000008:administration & dosage / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000008:administration & dosage / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D016559:Tacrolimus / Q000008:administration & dosage; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology
chemical_list: D016827:CD8 Antigens; D000939:Epitopes; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C483883:P18-I10 peptide; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C514797:gp160 protein, Human immunodeficiency virus 1; D016572:Cyclosporine; D016559:Tacrolimus