Directly transfected langerin+ dermal dendritic cells potentiate CD8+ T cell responses following intradermal plasmid DNA immunization.
Dendritic cells (DCs) play a critical role in CD8(+) T cell priming following DNA vaccination. In contrast to other DNA injection routes or immunization with viral vectors, Ag presentation is delayed following needle injection of plasmid DNA into the skin. The contribution of various skin DC subsets to this process is not known. In this study, we show that dermal CD11c(+) cells are the most important transgene-expressing cells following immunization. Using langerin- diphtheria toxin receptor mice we demonstrated that langerin(+) dermal DCs (Ln(+) dDCs) were crucial for generating an optimal CD8(+) T cell response. Blocking migration of skin cells to the lymph node (LN) ablated immunogenicity, suggesting that migration of dDC subsets to the LN is essential for generating immunity. This migration generated a weak Ag-presenting activity in vivo until day 5 postimmunization, which then increased dramatically. We further found that Ln(+) dDCs and dDCs were the only DC populations directly presenting Ag to CD8(+) T cells ex vivo during the initial 8-d period postimmunization. This activity changed on the following days, when both skin DCs and LN-resident DCs were able to present Ag to CD8(+) T cells. Taken together, our in vivo and ex vivo results suggest that activation of CD8(+) T cells following intradermal plasmid DNA immunization depends on directly transfected Ln(+)dDCs and dDCs. Moreover, the type of DCs presenting Ag changed over time, with Ln(+)dDCs playing the major role in potentiating the initial CD8(+) T cell response.
Elnekave
Mazal
M
Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel.
Furmanov
Karina
K
Nudel
Itay
I
Arizon
Moran
M
Clausen
Björn E
BE
Hovav
Avi-Hai
AH
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics*; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000008:administration & dosage / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D055879:Gene Knock-In Techniques; D006801:Humans; D007271:Injections, Intradermal; D037181:Lectins, C-Type / Q000096:biosynthesis* / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D037241:Mannose-Binding Lectins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010957:Plasmids / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014162:Transfection / Q000379:methods*
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D004279:DNA, Viral; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins