title: Infection of mouse bone marrow-derived dendritic cells with recombinant adenovirus vectors leads to presentation of encoded antigen by both MHC class I and class II molecules-potential benefits in vaccine design.
abstract: Dendritic cells (DCs) are highly specialised antigen-presenting cells (APCs) that are essential for the initiation and modulation of T cell-mediated immune responses. In order to induce effective CTL responses against most infections and tumours, DCs must prime both CD4(+) and CD8(+) antigen-specific T cells. It is, therefore, important in vaccine design to produce antigen-delivery systems that lead to the simultaneous presentation of multiple histocompatibility complex (MHC) class I- and class II-restricted antigenic peptides by DCs. In this study, the infection of immature mouse bone marrow-derived DCs (BMDCs) with recombinant adenovirus (rAd) vectors led to a marked upregulation of surface costimulatory molecules, IL-12 p40 production and capacity to stimulate both allogeneic and antigen-specific T cells. Furthermore, infection of immature and mature BMDCs with a rAd encoding chicken ovalbumin (OVA) led to presentation of the antigen to TCR-transgenic OVA-specific CD4(+) and CD8(+) T cells. In addition, the activation state of responding CD8(+) T cells was further amplified if they recognised antigen on rAd-transduced BMDCs in the presence of antigen-specific CD4(+) T cells. The results suggest that rAd-encoded OVA protein is secreted by BMDCs, taken up by endocytosis and presented in association with MHC class II molecules for activation of OVA-specific CD4(+) T cells. Consequently, rAd-transduced immature BMDCs become better stimulators of antigen-specific CD4(+) T cells than rAd-infected mature BMDCs. Taken together, these data have important implications for vaccine design, and suggest that infection of immature DCs with rAd encoding MHC class I and class II-restricted T cell epitopes could be an efficient means of inducing effective immune responses.
authors.affiliation: Department of Immunology, Imperial College of Science, Technology and Medicine (ICSTM), The Hammersmith Hospital, Du Cane Road, W12 ONN, London, UK.
authors.forename: Osquel Barroso
authors.initials: OB
authors.lastname: Herrera
authors.forename: Sara
authors.initials: S
authors.lastname: Brett
authors.forename: Robert I
authors.initials: RI
authors.lastname: Lechler
mesh_terms: D000256:Adenoviridae; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001854:Bone Marrow Cells / Q000276:immunology* / Q000821:virology; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology; D014162:Transfection
chemical_list: D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin