Nasal Flt3 ligand cDNA elicits CD11c+CD8+ dendritic cells for enhanced mucosal immunity.
Nasal immunization is an effective way to induce both mucosal and systemic immune responses. In this study, we assessed a cDNA vector for Flt3 ligand (FL) for its potential to enhance mucosal immunity or tolerance. Interestingly, tolerance was avoided and elevated levels of OVA-specific Ab responses were induced in nasal washes, fecal extracts, and saliva as well as in plasma when compared with mice given nasal OVA plus DNA plasmid without the FL gene. In addition, significant levels of OVA-specific CD4+ T cell proliferative responses and OVA-induced IL-4 and IL-2 production were noted in spleen and cervical lymph nodes. Further, marked increases in FL protein occurred in the nasal lamina propria and submandibular glands and the frequencies of CD11c+CD8+ dendritic cells (DCs) significantly increased in the mucosal tissues. Moreover, these DCs expressed high levels of CD40, CD80, CD86, and MHC class II molecules. Nasal delivery of plasmid FL with OVA resulted in FL expression in both mucosal inductive and effector sites and resulted in expanded activated lymphoid DCs. Thus, nasal plasmid FL prevents mucosal tolerance and enhances active immunity when given by a mucosal route.
Department of Oral Biology, Immunobiology Vaccine Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Kosuke
K
Kataoka
Jerry R
JR
McGhee
Ryoki
R
Kobayashi
Keiko
K
Fujihashi
Satoshi
S
Shizukuishi
Kohtaro
K
Fujihashi
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000281:Administration, Intranasal; D000818:Animals; D039521:CD11c Antigen / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000096:biosynthesis*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005822:Genetic Vectors; D018928:Immunity, Mucosal / Q000235:genetics; D007070:Immunoglobulin A / Q000096:biosynthesis; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D039521:CD11c Antigen; D016827:CD8 Antigens; D016207:Cytokines; D018076:DNA, Complementary; D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D008024:Ligands; D008565:Membrane Proteins; D019444:Vaccines, DNA; C084881:flt3 ligand protein; D010047:Ovalbumin