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Generation of specific Th1 and CD8+ T-cell responses by immunization with mouse CD8+ dendritic cells loaded with HIV-1 viral lysate or envelope glycoproteins
Authors:Aline Fleur  Brand Denys  Bout Daniel  Pierre Josette  Fouquenet Delphine  Verrier Bernard  Dimier-Poisson Isabelle
Affiliation:1. Pharmaceutical Technology, Te. Far. T. I. group, Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Italy;2. Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy;3. WG Molecular Analysis of Synaptopathies, Neurology Dept., Neurocenter of Ulm University, Ulm, Germany;4. Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany
Abstract:Immunization with antigen-pulsed dendritic cells (DCs) can be used to elicit optimal immune responses. We developed the SRDC cell line, with a morphology, phenotype and activity similar to mouse splenic CD4(-)CD8alpha(+)CD205(+)CD11b(-) dendritic cells, which induce a polarized Th1 immune response. We evaluated the ability of SRDCs pulsed with HIV-1 viral lysate, oligomeric soluble gp140 or capsid p24 to induce specific antibody and T-cell responses in CBA/J mice. Immunization with all loaded SRDCs elicited antibody responses against the antigens tested. However, only HIV-1 viral lysate and gp140-pulsed SRDCs elicited specific CD4(+) and CD8(+) T-cell responses. These findings demonstrate the value of well characterized DC lines for optimizing the antigen-loading mixture, according to the DC population targeted. Our data suggest that splenic DCs pulsed with complex antigens, such as HIV-1 viral lysate or oligomeric soluble gp140, could be used as vaccines, eliciting strong primary Th1-polarized and humoral immune responses against HIV proteins in vivo.
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