TY - JOUR
T1 - Keratinocytes function as accessory cells for presentation of endogenous antigen expressed in the epidermis
AU - Kim, Brian S.
AU - Miyagawa, Fumi
AU - Cho, Young Hun
AU - Bennett, Clare L.
AU - Clausen, Björn E.
AU - Katz, Stephen I.
N1 - Funding Information:
We thank Jay Linton for his excellent technical expertise, Dr Xu Feng and Dr Takashi Kakinuma for helpful suggestions, and Dr Mark Udey for critical discussions and review of the paper. This study was supported in part by the Center for Cancer Research Intramural Research Program, NCI, NIH, and by the Landsteiner Foundation for Blood Transfusion Research (LSBR) (BEC) and a VIDI fellow of The Netherlands Organization for Scientific Research (NWO) (BEC).
PY - 2009
Y1 - 2009
N2 - 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 (Vα2/Vβ5) 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 × 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 β 2-microglobulin-deficient (β 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 β 2 m → K14-OVA × 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.
AB - 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 (Vα2/Vβ5) 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 × 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 β 2-microglobulin-deficient (β 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 β 2 m → K14-OVA × 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.
UR - http://www.scopus.com/inward/record.url?scp=79958086561&partnerID=8YFLogxK
U2 - 10.1038/jid.2009.176
DO - 10.1038/jid.2009.176
M3 - Article
C2 - 19554018
AN - SCOPUS:79958086561
SN - 0022-202X
VL - 129
SP - 2805
EP - 2817
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 12
ER -