title: Langerhans cells are precommitted to immune tolerance induction.
abstract: Antigen-dependent interactions between T lymphocytes and dendritic cells (DCs) can produce two distinct outcomes: tolerance and immunity. It is generally considered that all DC subsets are capable of supporting both tolerogenic and immunogenic responses, depending on their exposure to activating signals. Here, we tested whether epidermal Langerhans cells (LCs) can support immunogenic responses in vivo in the absence of antigen presentation by other DC subsets. CD4 T cells responding to antigen presentation by activated LCs initially proliferated but then failed to differentiate into effector/memory cells or to survive long term. The tolerogenic function of LCs was maintained after exposure to potent adjuvants and occurred despite up-regulation of the costimulatory molecules CD80, CD86, and IL-12, but was consistent with their failure to translocate the NF-κB family member RelB from the cytoplasm to the nucleus. Commitment of LCs to tolerogenic function may explain why commensal microorganisms expressing Toll-like receptor (TLR) ligands but confined to the skin epithelium are tolerated, whereas invading pathogens that breach the epithelial basement membrane and activate dermal DCs stimulate a strong immune response.
authors: T Cell Biology Research Program, Centenary Institute of Cancer Medicine and Cell Biology, Newtown NSW 2042, Australia.
authors: Elena
authors: E
authors: Shklovskaya
authors: Brendan J
authors: BJ
authors: O'Sullivan
authors: Lai Guan
authors: LG
authors: Ng
authors: Ben
authors: B
authors: Roediger
authors: Ranjeny
authors: R
authors: Thomas
authors: Wolfgang
authors: W
authors: Weninger
authors: Barbara
authors: B
authors: Fazekas de St Groth
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice
chemical_list: D015703:Antigens, CD