DNA vaccines, combining form of antigen and method of delivery to raise a spectrum of IFN-gamma and IL-4-producing CD4+ and CD8+ T cells.
DNA-based immunizations have been used to determine the patterns of type 1 and type 2 cytokines that can be induced in vivo for Ag-specific CD4(+) and CD8(+) T cells. IL-4 was used as a signature cytokine for a type 2 T cell response and IFN-gamma as the signature cytokine for a type 1 response. Gene gun deliveries of secreted Ags were used to bias responses toward type 2 and saline injections of cell-associated Ags to bias responses toward type 1. The studies revealed that gene gun bombardments of DNAs expressing secreted Ags strongly biased responses toward type 2, inducing IL-4-producing CD8(+) as well as CD4(+) T cells. Saline injections of DNAs expressing cell-associated Ags strongly biased responses toward type 1, inducing IFN-gamma-producing CD8(+) and CD4(+) cells. A mixed type 1/type 2 response of IFN-gamma-producing CD8(+) T cells and IL-4-producing CD4(+) T cells was found for gene gun deliveries of cell-associated Ags. Saline injections of secreted Ags raised a weakly type 1-biased response characterized by only slightly higher frequencies of IFN-gamma- than IL-4-producing CD4(+) and CD8(+) T cells. Studies in B cell knockout and hen egg lysozyme Ig transgenic mice revealed that B cells were required for the generation of IL-4-producing CD8(+) T cells.
Oran
Alp E
AE
Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Robinson
Harriet L
HL
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019470:Biolistics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016601:RNA-Binding Proteins; D012965:Sodium Chloride / Q000008:administration & dosage; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D015847:Interleukin-4; D012965:Sodium Chloride; D007371:Interferon-gamma; D010047:Ovalbumin