Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis.
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.
Kim
Brian S
BS
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Miyagawa
Fumi
F
Cho
Young-Hun
YH
Bennett
Clare L
CL
Clausen
Björn E
BE
Katz
Stephen I
SI
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
D004167:Diphtheria Toxin; D010047:Ovalbumin