1. ¹Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
2. ²Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, Maryland, USA
3. ³Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, AZ Amsterdam, The Netherlands
4. ⁴Department of Immunology, Erasmus University Medical Center, GE Rotterdam, The Netherlands

Correspondence: Dr Stephen I. Katz, Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. E-mail: katzs@od.niams.nih.gov

Received 10 January 2009; Revised 27 March 2009; Accepted 22 April 2009; Published online 25 June 2009.

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 (V2/V5) 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 ₂-microglobulin-deficient (₂m) 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 ₂m 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.

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