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.
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.
Aline
Fleur
F
Université François Rabelais, INRA, UMR 0483 Université-INRA d'Immunologie Parasitaire et Vaccinologie, IFR Agents transmissibles en Infectiologie, UFR des Sciences Pharmaceutiques, 31 avenue Monge, 37200 Tours, France.
Brand
Denys
D
Bout
Daniel
D
Pierre
Josette
J
Fouquenet
Delphine
D
Verrier
Bernard
B
Dimier-Poisson
Isabelle
I
D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D016655:HIV Core Protein p24 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus
D015686:Gene Products, env; D016655:HIV Core Protein p24; D014759:Viral Envelope Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma