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Journal of Virology, December 1999, p. 10281-10288, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Transfer of Human CD4+ T Lymphocytes Producing Beta Interferon in Hu-PBL-SCID Mice Controls Human Immunodeficiency Virus Infection

Vincent Vieillard,1,dagger Stephane Jouveshomme,2 Nicole Leflour,2 Eric Jean-Pierre,2 Patrice Debre,2 Edward De Maeyer,1 and Brigitte Autran2,*

Equipe de Génétique des Cytokines, UMR CNRS 146, Institut Curie, Orsay,1 and Laboratoire d'Immunologie Cellulaire et Tissulaire, UMR CNRS 7627, Hopital Pitie-Salpêtrière, Paris,2 France

Received 3 March 1999/Accepted 3 September 1999

Beta interferon (IFN-beta ) exerts pleiotropic antiretroviral activities and affects many different stages of the human immunodeficiency virus (HIV) infectious cycle in IFN-treated cells. To explore whether transfer of genetically engineered human CD4+ T cells producing constitutively low amounts of IFN-beta can eradicate HIV in vivo, we developed a new Hu-PBL-SCID mouse model supporting a persistent, replicative HIV infection maintained by periodic reinoculations of activated human CD4+ T cells. Transferring human CD4+ T cells containing the IFN-beta retroviral vector drastically reduced the preexisting HIV infection and enhanced CD4+ T-cell survival and Th1 cytokine expression. Furthermore, in 40% of the Hu-PBL-SCID mice engrafted with IFN-beta -transduced CD4+ T cells, HIV-1 was undetectable in vivo as well as after cocultivation of mouse tissues with human phytohemagglutinin-stimulated lymphoblasts. These results indicate that a therapeutic strategy based upon IFN-beta transduction of CD4+ T cells may be an approach to controlling a preexisting HIV infection and allowing immune restoration.

* Corresponding author. Mailing address: Laboratoire d'Immunologie Cellulaire et Tissulaire, UMR CNRS 7627, Hopital Pitie-Salpêtrière, 83 Blvd. de l'Hôpital, 75013 Paris, France. Phone: 33-1-42-17-74-03. Fax: 33-1-42-17-74-90. E-mail: brigitte.autran{at}psl.ap-hop-paris.fr.

dagger Present address: Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.

Journal of Virology, December 1999, p. 10281-10288, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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