Characterization of the type immune responses using different forms of antigen and different methods of DNA vaccination.

摘要

DNA-based immunizations have been used to determine the patterns of type 1 and type 2 cytokines that can be induced in vivo for antigen-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 antigens were used to bias responses towards type 2 and saline injections of cell-associated antigens to bias responses towards type 1. The studies revealed that gene gun bombardments of DNAs expressing secreted antigens strongly biased responses towards type 2, inducing IL-4-producing CD8+ as well as CD4+ T cells. Saline injections of DNAs expressing cell-associated antigens strongly biased responses towards 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 antigens. Saline injections of secreted antigens 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 knock out and hen egg lysozyme Ig transgenic mice revealed that B cells were required for the generation of IL-4-producing CD8+ T cells. When mice vaccinated with these different constructs were challenged with live influenza A virus, the IL-4 biased responses were lost in the CD8+ T cell compartment and replaced with peptide-specific IFN-γ-dominant responses. Our results suggest that although T cell responses can be tailored by DNA vaccination with varying forms of antigen, after live viral challenge, the type of T cell response that is expanded is the one best suited at coping with the viral infection, especially at the site of infection.