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.
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.
Hadida
F
F
Laboratoire d'Immunologie Cellulaire, UMR 7627 CNRS, Hôpital Pitié-Salpétrière, Paris, France. Hadida@ccr.jussieu.fr
De Maeyer
E
E
Cremer
I
I
Autran
B
B
Baggiolini
M
M
Debré
P
P
Vieillard
V
V
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
D018946:Chemokine CCL5; D019707:Receptors, Chemokine; D016899:Interferon-beta