Skin-derived dendritic cells can mediate deletional tolerance of class I-restricted self-reactive T cells.
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.
Waithman
Jason
J
Department of Microbiology and Immunology, University of Melbourne, Parkville, Australia.
Allan
Rhys S
RS
Kosaka
Hiroshi
H
Azukizawa
Hiroaki
H
Shortman
Ken
K
Lutz
Manfred B
MB
Heath
William R
WR
Carbone
Francis R
FR
Belz
Gabrielle T
GT
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007801:Langerhans Cells / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D010047:Ovalbumin