Langerhans cells suppress contact hypersensitivity responses via cognate CD4 interaction and langerhans cell-derived IL-10.
Mice lacking epidermal Langerhans cells (LC) develop exaggerated contact-hypersensitivity (CHS) responses due to the absence of LC during sensitization/initiation. Examination of T cell responses reveals that the absence of LC leads to increased numbers of hapten-specific CD4 and CD8 T cells but does not alter cytokine expression or development of T regulatory cells. CHS responses and Ag-specific T cells are increased in mice in which MHC class II is ablated specifically in LC suggesting that direct cognate interaction between LC and CD4 cells is required for suppression. LC-derived IL-10 is also required for optimal inhibition of CHS. Both LC-derived IL-10-mediated suppression and full LC activation require LC expression of MHC class II. These data support a model in which cognate interaction of LC with CD4 T cells enables LC to inhibit expansion of Ag-specific responses via elaboration of IL-10.
Igyarto
Botond Z
BZ
Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA.
Jenison
Matthew C
MC
Dudda
Jan C
JC
Roers
Axel
A
Müller
Werner
W
Koni
Pandelakis A
PA
Campbell
Daniel J
DJ
Shlomchik
Mark J
MJ
Kaplan
Daniel H
DH
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003877:Dermatitis, Contact / Q000276:immunology* / Q000378:metabolism; D004139:Dinitrofluorobenzene / Q000276:immunology / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D012867:Skin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; C064658:RAG-1 protein; D016753:Interleukin-10; D004139:Dinitrofluorobenzene