Skin-derived dendritic cells induce potent CD8(+) T cell immunity in recombinant lentivector-mediated genetic immunization.
The skin contains readily accessible dendritic cells (DCs) with potent antigen presentation function and functional plasticity enabling the integration of antigen specificity with environmentally responsive immune control. Recent studies challenge the established paradigm of cutaneous immune function by suggesting that lymph node-resident DCs, rather than skin-derived DCs (sDCs), are responsible for eliciting T cell immunity against cutaneous pathogens including viral vectors. We show that cutaneous delivery of lentivirus results in direct transfection of sDCs and potent and prolonged antigen presentation. Further, sDCs are the predominant antigen-presenting cells for the induction of potent and durable CD8(+) T cell immunity. These results support the classical paradigm of cutaneous immune function and suggest that antigen presentation by sDCs contributes to the high potency of lentivector-mediated genetic immunization.
He
Yukai
Y
Department of Dermatology, University of Pittsburgh School of Medicine, Suite 145 Lothrop Hall, 190 Lothrop Street, Pittsburgh, Pennsylvania 15213, USA. ykhe@pitt.edu
Zhang
Jiying
J
Donahue
Cara
C
Falo
Louis D
LD
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D019470:Biolistics; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D005822:Genetic Vectors; D007114:Immunization / Q000379:methods*; D016086:Lentivirus / Q000235:genetics / Q000276:immunology*; D016180:Lentivirus Infections / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000276:immunology* / Q000821:virology; D014162:Transfection
D011994:Recombinant Proteins