Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells.
The initiation of an adaptive immune response requires Ag presentation in combination with the appropriate activation signals. Classically, Ag presentation and immune activation occur in the lymph node and spleen, where a favorable organ architecture and rich cellular help can enhance the process. Recently, several investigators have reported the use of DNA expression cassettes to elicit cellular and humoral immunity against diverse pathogens. Although the immune mechanisms involved are still poorly understood, plasmid inoculation represents a model system for studying immune function in response to invading pathogens. In this report, we demonstrate the presence of activated macrophages or dendritic cells in the blood lymphocyte pool and peripheral tissues of animals inoculated with DNA expression cassettes. These cells are directly transfected in vivo, present Ag, and display the surface proteins CD80 and CD86. Our studies indicate that these cells function as APC and can activate naive T lymphocytes. They may represent an important first step APC in genetic immunization and natural infection.
Chattergoon
M A
MA
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Robinson
T M
TM
Boyer
J D
JD
Weiner
D B
DB
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D002455:Cell Division; D005260:Female; D005434:Flow Cytometry; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014162:Transfection / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D015685:Fusion Proteins, gag-pol; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D019444:Vaccines, DNA; D000099192:CD69 Antigens; C497965:Cd86 protein, mouse