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

2007; American Association of Immunologists; Volume: 179; Issue: 7 Linguagem: Inglês

10.4049/jimmunol.179.7.4535

1550-6606

Jason Waithman, Rhys S. Allan, Hiroshi Kosaka, Hiroaki Azukizawa, Ken Shortman, Manfred B. Lutz, William R. Heath, Federico Carbone, Gabrielle T. Belz,

Immune Cell Function and Interaction

Abstract 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.