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. |
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Authors: | F Hadida E De Maeyer I Cremer B Autran M Baggiolini P Debré V Vieillard |
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Affiliation: | Laboratoire d'Immunologie Cellulaire, UMR 7627 CNRS, H?pital Pitié-Salpétrière, Paris, France. Hadida@ccr.jussieu.fr |
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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. |
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