title: Acquired constitutive expression of interferon beta after gene transduction enhances human immunodeficiency virus type 1-specific cytotoxic T lymphocyte activity by a RANTES-dependent mechanism.
abstract: CTL lines directed against HIV-1 antigens were generated from infected individuals and were transduced by the HMB-K(b)HuIFNbeta vector, resulting in low, constitutive expression of interferon beta (IFN-beta). The IFN-beta-transduced cells showed markedly increased HIV-1-specific, MHC class I-restricted CTL activity against HIV-1-LAI Gag, Pol, or Env antigens. This effect of IFN-beta was correlated with an overexpression of RANTES and completely abrogated by RANTES-blocking antibody. The present results provide the first evidence that IFN-beta transduction of CTL lines enhances HIV-specific cytotoxic activities through an upregulation of RANTES production. The efficient elimination of HIV-infected cells by IFN-beta-transduced CTL lines makes this gene therapy approach an attractive treatment for AIDS.
authors.affiliation: Laboratoire d'Immunologie Cellulaire, UMR 7627 CNRS, Hôpital Pitié-Salpétrière, Paris, France. Hadida@ccr.jussieu.fr
authors.forename: F
authors.initials: F
authors.lastname: Hadida
authors.forename: E
authors.initials: E
authors.lastname: De Maeyer
authors.forename: I
authors.initials: I
authors.lastname: Cremer
authors.forename: B
authors.initials: B
authors.lastname: Autran
authors.forename: M
authors.initials: M
authors.lastname: Baggiolini
authors.forename: P
authors.initials: P
authors.lastname: Debré
authors.forename: V
authors.initials: V
authors.lastname: Vieillard
mesh_terms: D018946:Chemokine CCL5 / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014161:Transduction, Genetic
chemical_list: D018946:Chemokine CCL5; D019707:Receptors, Chemokine; D016899:Interferon-beta