Transfer of human CD4(+) T lymphocytes producing beta interferon in Hu-PBL-SCID mice controls human immunodeficiency virus infection.
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.
Vieillard
V
V
Equipe de Génétique des Cytokines, UMR CNRS 146, Institut Curie, Orsay, France.
Jouveshomme
S
S
Leflour
N
N
Jean-Pierre
E
E
Debre
P
P
De Maeyer
E
E
Autran
B
B
D000818:Animals; D019380:Anti-HIV Agents / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D016899:Interferon-beta / Q000235:genetics / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D018448:Models, Immunological; D018417:Th1 Cells / Q000276:immunology
D019380:Anti-HIV Agents; D016207:Cytokines; D016899:Interferon-beta