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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.
AuthorsOsquel Barroso Herrera, Sara Brett, Robert I Lechler
JournalVaccine (Vaccine) Vol. 21 Issue 3-4 Pg. 231-42 (Dec 13 2002) ISSN: 0264-410X [Print] Netherlands
PMID12450698 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Recombinant Fusion Proteins
  • Ovalbumin
Topics
  • Adenoviridae
  • Animals
  • Antigen Presentation (genetics)
  • Bone Marrow Cells (immunology, virology)
  • Bone Marrow Transplantation
  • CD4-Positive T-Lymphocytes (immunology)
  • Cells, Cultured
  • Dendritic Cells (immunology, metabolism, transplantation)
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Vectors (chemical synthesis, immunology)
  • HLA-DR Antigens (genetics)
  • Histocompatibility Antigens Class I (immunology)
  • Histocompatibility Antigens Class II (immunology)
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin (pharmacology)
  • Recombinant Fusion Proteins (analysis, immunology)
  • Transfection

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