title: Langerin+ dermal DC, but not Langerhans cells, are required for effective CD8-mediated immune responses after skin scarification with vaccinia virus.
abstract: Skin scarification (s.s.) with vaccinia virus (VACV) is essential for generation of an optimal protective T-cell memory immune response. Dendritic cells (DCs), which are professional antigen-presenting cells, are required for naive T-cell priming and activation. At least three subsets of skin-resident DC have been identified: Langerhans cells (LCs), dermal Langerin+ DC (Lang+ dDC), and dermal Langerin- DC (Lang- dDC). Using Langerin-diphtheria toxin receptor mice and established mouse model of VACV delivered by s.s., we demonstrated that Lang+ dDC, but not LC, are absolutely required for the induction of a rapid and robust antigen-specific CD8+ T-cell response after s.s. with VACV. The depletion of Lang+ dDC led to a significant delay in the priming and proliferation of antigen-specific CD8+ T cells. Moreover, CD8+ T cells generated after VACV s.s. in the absence of Lang+ dDC lacked effector cytotoxic functions both in vitro and in vivo. While s.s.-immunized wild-type and LC-depleted mice controlled the progression of OVA257-264 expressing T-cell lymphoma EG7 (injected intradermally), the depletion of Lang+ dDC led to rapid lymphoma progression and mortality. These data indicate that of all skin DC subsets, Lang+ dDC is the most critical for the generation of robust CD8+ T-cell immunity after s.s. with VACV.
authors.affiliation: Department of Dermatology, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Dermatology and Pediatric Dermatology, INSERM U1035, Bordeaux, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Seneschal
authors.affiliation: Department of Dermatology, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: tkupper@partners.org.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Kupper
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002921:Cicatrix / Q000276:immunology / Q000821:virology; D020405:Dermis / Q000166:cytology / Q000276:immunology / Q000821:virology; D005260:Female; D007114:Immunization / Q000379:methods; D007156:Immunologic Memory / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000276:immunology / Q000293:injuries / Q000821:virology; D012899:Smallpox / Q000276:immunology*; D012900:Smallpox Vaccine / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D012900:Smallpox Vaccine