The role of skin-derived dendritic cells in CD8+ T cell priming following immunization with lentivectors.
Although skin dendritic cells (DCs) have been shown to directly present Ag to CD8(+) T cells after intradermal immunization with lentivectors, the contribution of the different skin DC subsets to this process remains unclear. Using langerin-diphtheria toxin receptor transgenic mice we demonstrated that ablation of langerhans cells and langerin-expressing positive dermal DCs (Ln(+)dDCs) did not interfere with the generation of CD8(+) T cells by lentiviral vectors. Consistent with these findings, the absence of langerhans cells and Ln(+)dDCs did not hamper the presentation level of lentiviral-derived Ag by skin DCs in vitro. We further demonstrated that only dDCs and Ln(+)dDCs were capable of presenting Ag, however, the number of dDCs migrating to the draining lymph nodes was 6-fold higher than that of Ln(+)dDCs. To study how the duration of DC migration influences CD8(+) T cell responses, we analyzed the kinetics of Ag expression at the injection site and manipulated DC migration by excising the injected skin at various times after immunization. A low level of Ag expression was seen 1 wk after the immunization; peaked during week 2, and was considerably cleared by week 3 via a perforin-dependent fas-independent mechanism. Removing the injection site 3 or 5 d, but not 10 d, after the immunization, resulted in a reduced CD8(+) T cell response. These findings suggest that dDCs are the main APCs active after intradermal lentiviral-mediated immunization, and migration of dDCs in the initial 10-d period postimmunization is required for optimal CD8(+) T cell induction.
Furmanov
Karina
K
Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel.
Elnekave
Mazal
M
Lehmann
Dan
D
Clausen
Bjorn E
BE
Kotton
Darrell N
DN
Hovav
Avi-Hai
AH
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D055879:Gene Knock-In Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012867:Skin / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*
D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D014765:Viral Vaccines