IL-10-producing Langerhans cells and regulatory T cells are responsible for depressed contact hypersensitivity in grafted skin.
Although skin grafting is a common surgical technique, the immunological state of grafted skin remains unelucidated. An experimental model has shown that the development of murine contact hypersensitivity (CHS) is depressed when mice are sensitized with a hapten through full-thickness grafted skin. We explored the immunological mechanisms underlying this hyposensitization, focusing on the fate of Langerhans cells (LCs). When FITC was applied to grafted skin, FITC-bearing LCs were capable of migrating to the draining lymph nodes. Epidermal cell suspensions isolated from the grafted skin produced a high amount of IL-10 as assessed by real-time PCR. Adoptive transfer of immune lymph node cells from the sensitized mice suppressed the CHS response of recipients in an antigen-specific manner. CD4(+)CD25(+) but not CD4(+)CD25(-) T cells purified from lymph node cells were responsible for this suppression. Finally, we detected high expression of receptor activators of nuclear factor kappa-B ligand (RANKL) in the grafted skin, and found that recombinant RANKL stimulated LCs to produce IL-10. These findings suggest that the hyposensitization of CHS through the grafted skin is not attributable merely to the reduction of LC number but that IL-10-producing LCs exert a downmodulatory effect by inducing regulatory T cells.
Yoshiki
Ryutaro
R
Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan. yockey@med.uoeh-u.ac.jp
Kabashima
Kenji
K
Sugita
Kazunari
K
Atarashi
Kenji
K
Shimauchi
Takatoshi
T
Tokura
Yoshiki
Y
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D003877:Dermatitis, Contact / Q000378:metabolism*; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D007801:Langerhans Cells / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D053245:RANK Ligand / Q000378:metabolism; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000378:metabolism*
D053645:Interleukin-2 Receptor alpha Subunit; D053245:RANK Ligand; D016753:Interleukin-10