DNA Vaccines, Combining Form of Antigen and Method of Delivery to Raise a Spectrum of IFN-γ and IL-4-Producing CD4+ and CD8+ T Cells

Abstract

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-γ 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-γ-producing CD8+ and CD4+ cells. A mixed type 1/type 2 response of IFN-γ-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-γ- 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.