Interferon beta transduction of peripheral blood lymphocytes from HIV-infected donors increases Th1-type cytokine production and improves the proliferative response to recall antigens.
We are developing a gene therapy method of HIV infection based on the constitutive low production of interferon (IFN) beta. Peripheral blood lymphocytes (PBL) from HIV-infected patients at different clinical stages of infection were efficiently transduced with the HMB-HbHuIFNbeta retroviral vector. The constitutive low production of IFN-beta in cultured PBL from HIV-infected patients resulted in a decreased viral production and an enhanced survival of CD4+ cells, and this protective effect was observed only in the PBL derived from donors having a CD4+ cell count above 200 per mm3. In IFN-beta-transduced PBL from healthy and from HIV-infected donors, the production of the Th1-type cytokines IFN-gamma and interleukin (IL)-12 was enhanced. In IFN-beta-transduced PBL from HIV-infected donors, the production of IL-4, IL-6, IL-10, and tumor necrosis factor alpha was maintained at normal levels, contrary to the increased levels produced by the untransduced PBL. The proliferative response to recall antigens was partially restored in IFN-beta-transduced PBL from donors with an impaired antigen response. Thus, in addition to inhibiting HIV replication, IFN-beta transduction of PBL from HIV-infected donors improves several parameters of immune function.
Vieillard
V
V
Unité Mixte de Recherche 177 Centre National de la Recherche Scientifique, Institut Curie, Université Paris 11, 91405 Orsay, France.
Cremer
I
I
Lauret
E
E
Rozenbaum
W
W
Debré
P
P
Autran
B
B
De Maeyer
E
E
D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae; D018417:Th1 Cells / Q000276:immunology*; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D016899:Interferon-beta; D007371:Interferon-gamma