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Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Dendritic cells (DC) play a pivotal role in the control of T cell immunity due to their ability to stimulate naive T cells and direct effector function. Murine and human DC are composed of a number of phenotypically, and probably developmentally, distinct subsets, which may play unique roles in the initiation and regulation of T cell responses. The skin is populated by at least two subsets of DC: Langerhans cells (LC), which form a contiguous network throughout the epidermis, and dermal DC. LC have classically been thought vital to initiate T cell responses to cutaneous Ags. However, recent data have highlighted the importance of dermal DC in cutaneous immunity, and the requirement for LC has become unclear. To define the relative roles of LC and dermal DC, we and others generated mouse models in which LC were specifically depleted in vivo. Unexpectedly, these studies yielded conflicting data as to the role of LC in cutaneous contact hypersensitivity (CHS). Extending our initial finding, we demonstrate that topical Ag is inefficiently transported to draining lymph nodes in the absence of LC, resulting in suboptimal priming of T cells and reduced CHS. However, dermal DC may also prime cutaneous T cell responses, suggesting redundancy between the two different skin DC subsets in this model.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by a Dutch Research Foundation (NWO) post-doctoral fellowship to C.L.B. (VENI 916-56-169), and a Landsteiner Foundation for Blood Transfusion Research career development grant to B.E.C. (0414).
2 Current address: Department of Haematology, Royal Free and University College Medical School, Rowland Hill Street, London, U.K.
3 Address correspondence and reprint requests to Dr. Björn Clausen, Academic Medical Center, University of Amsterdam, Meibergdreef 15, Amsterdam, The Netherlands. E-mail address: b.e.clausen{at}amc.uva.nl
4 Abbreviations used in this paper: DC, dendritic cell; LN, lymph nodes; DT, diphtheria toxin; DTR, DT receptor; CHS, contact hypersensitivity; AOO, acetone/olive oil; wt, wild type.
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