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Skin-Derived Dendritic Cells Can Mediate Deletional Tolerance of Class I-Restricted Self-Reactive T Cells¹

Jason Waithman^*, Rhys S. Allan^*, Hiroshi Kosaka, Hiroaki Azukizawa, Ken Shortman, Manfred B. Lutz^¶, William R. Heath^2,, Francis R. Carbone^2,* and Gabrielle T. Belz

^* Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia; Department of Dermatology, National Hospital Organization, Osaka Minami Medical Centre, Kawachinagano, Japan; Department of Dermatology, Osaka University Medical School, Suita, Japan; Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; and ^¶ Institute for Virology and Immunobiology, University of Wuerzburg, D-97078 Wuerzburg, Germany

Skin-draining lymph nodes contain a number of dendritic cell (DC) subsets of different origins. Some of these are migratory, such as the skin-derived epidermal Langerhans cells and a separate dermal DC subset, whereas others are lymphoid resident in nature, such as the CD8⁺ DCs found throughout the lymphoid tissues. In this study, we examine the DC subset presentation of skin-derived self-Ag by migratory and lymphoid-resident DCs, both in the steady state and under conditions of local skin infection. We show that presentation of self-Ag is confined to skin-derived migrating DCs in both settings. Steady state presentation resulted in deletional T cell tolerance despite these DCs expressing a relatively mature phenotype as measured by traditional markers such as the level of MHC class II and CD86 expression. Thus, self-Ag can be carried to the draining lymph nodes by skin-derived DCs and there presented by these same cells for tolerization of the circulating T cell pool.

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 grants from the Australian National Heath and Medical Research Council, The Wellcome Trust, and the Howard Hughes Medical Institute.

² Address correspondence and reprint requests to Dr. William R. Heath, Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Australia; E-mail address: heath{at}wehi.edu.au or Dr. Francis R. Carbone, Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia; E-mail address: fcarbone{at}unimelb.edu.au

³ Abbreviations used in this paper: DC, dendritic cell; LN, lymph node; PI, propidium iodide.

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