Keratinocytes Function as Accessory Cells for Presentation of Endogenous Antigen Expressed in the Epidermis
The Journal of Investigative Dermatology , Volume 129 - Issue 12 p. 2805- 2817
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 β2-microglobulin-deficient (β2m) 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 β2m → 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.Journal of Investigative Dermatology advance online publication, 25 June 2009; doi:10.1038/jid.2009.176.
|The Journal of Investigative Dermatology|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Kim, B.S, Miyagawa, F, Cho, Y.H, Bennett, C.L, Clausen, B.E, & Katz, S.I. (2009). Keratinocytes Function as Accessory Cells for Presentation of Endogenous Antigen Expressed in the Epidermis. The Journal of Investigative Dermatology, 129(12), 2805–2817. doi:10.1038/jid.2009.176