PMID- 24126845 OWN - NLM STAT- MEDLINE DCOM- 20140409 LR - 20211021 IS - 1523-1747 (Electronic) IS - 0022-202X (Print) IS - 0022-202X (Linking) VI - 134 IP - 3 DP - 2014 Mar TI - Langerin+ dermal DC, but not Langerhans cells, are required for effective CD8-mediated immune responses after skin scarification with vaccinia virus. PG - 686-694 LID - S0022-202X(15)36653-7 [pii] LID - 10.1038/jid.2013.418 [doi] AB - 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. FAU - Seneschal, Julien AU - Seneschal J AD - 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. FAU - Jiang, Xiaodong AU - Jiang X AD - Department of Dermatology, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA. FAU - Kupper, Thomas S AU - Kupper TS AD - Department of Dermatology, Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA. Electronic address: tkupper@partners.org. LA - eng GR - R01 AI041707/AI/NIAID NIH HHS/United States GR - R01 AI097128/AI/NIAID NIH HHS/United States GR - R01 AR065807/AR/NIAMS NIH HHS/United States GR - 5R01-AI-041707-15/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131014 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Antigens, Surface) RN - 0 (Cd207 protein, mouse) RN - 0 (Lectins, C-Type) RN - 0 (Mannose-Binding Lectins) RN - 0 (Smallpox Vaccine) SB - IM MH - Adoptive Transfer MH - Animals MH - Antigens, Surface/immunology/metabolism MH - CD8-Positive T-Lymphocytes/*immunology/metabolism/virology MH - Cicatrix/immunology/virology MH - Dermis/cytology/immunology/virology MH - Female MH - Immunization/methods MH - Immunologic Memory/*immunology MH - Langerhans Cells/*immunology/metabolism/virology MH - Lectins, C-Type/immunology/metabolism MH - Mannose-Binding Lectins/immunology/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Skin/immunology/injuries/virology MH - Smallpox/*immunology MH - Smallpox Vaccine/*immunology MH - Vaccinia virus/*immunology PMC - PMC3945525 MID - NIHMS528938 COIS- CONFLICT OF INTEREST The authors state no conflict of interest. EDAT- 2013/10/16 06:00 MHDA- 2014/04/10 06:00 PMCR- 2014/09/01 CRDT- 2013/10/16 06:00 PHST- 2013/01/24 00:00 [received] PHST- 2013/09/11 00:00 [revised] PHST- 2013/09/13 00:00 [accepted] PHST- 2013/10/16 06:00 [entrez] PHST- 2013/10/16 06:00 [pubmed] PHST- 2014/04/10 06:00 [medline] PHST- 2014/09/01 00:00 [pmc-release] AID - S0022-202X(15)36653-7 [pii] AID - 10.1038/jid.2013.418 [doi] PST - ppublish SO - J Invest Dermatol. 2014 Mar;134(3):686-694. doi: 10.1038/jid.2013.418. Epub 2013 Oct 14.