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.
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.
Herrera
Osquel Barroso
OB
Department of Immunology, Imperial College of Science, Technology and Medicine (ICSTM), The Hammersmith Hospital, Du Cane Road, W12 ONN, London, UK.
Brett
Sara
S
Lechler
Robert I
RI
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
D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; D010047:Ovalbumin