title: Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis.
abstract: The precise contribution(s) of skin dendritic cells (DCs) to immune responses in the skin has not been well delineated. We developed an intradermal (i.d.) injection model in which CD8+ T (OT-I) cells that express ovalbumin (OVA) peptide-specific TCRs (Valpha2/Vbeta5) are delivered directly to the dermis of transgenic (Tg) mice expressing OVA in the epidermis. After i.d. injection, these mice reliably develop skin graft-versus-host disease (GVHD) by day 7. To determine the relative contribution of Langerhans cells (LCs) to the ensuing GVHD-like reaction, we generated K14-OVA x Langerin-diphtheria-toxin-receptor (Langerin-DTR) Tg mice to allow conditional ablation of LCs in the epidermis. To delineate the role of dermal DCs (dDCs) in the reaction, we also generated K14-OVA Tg chimeras using beta(2)-microglobulin-deficient (beta(2)m) congenic donor bone marrow cells. Dermal DCs in these mice cannot present OVA to autoreactive T cells (OT-I cells), whereas the LCs are antigen presentation-competent. Unexpectedly, OT-I cell injection into diphtheria toxin (DT)-treated beta(2)m --> K14-OVA x Langerin-DTR Tg mice resulted in skin GVHD. Thus, in vivo, both LC and dDC appear to be dispensable for the induction of keratinocyte-directed, CD8-mediated effector immune responses. Furthermore and surprisingly, OVA-expressing epidermal cells depleted of LCs that could not initiate allogeneic epidermal lymphocyte reactions activated naive OT-I cells in vitro. These results indicate that keratinocytes may function as accessory cells competent to prime naive skin-reactive T cells.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://network.nature.com/group/jidclub.
authors: Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Brian S
authors: BS
authors: Kim
authors: Fumi
authors: F
authors: Miyagawa
authors: Young-Hun
authors: YH
authors: Cho
authors: Clare L
authors: CL
authors: Bennett
authors: Björn E
authors: BE
authors: Clausen
authors: Stephen I
authors: SI
authors: Katz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology; D002460:Cell Line; D020405:Dermis / Q000166:cytology / Q000276:immunology; D004167:Diphtheria Toxin / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology*; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology
chemical_list: D004167:Diphtheria Toxin; D010047:Ovalbumin