Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10.
Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. RelB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which RelB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4+ T cells induced by the DCs transfer antigen-specific "infectious" tolerance to primed recipients in an interleukin-10-dependent fashion. Thus CD40, regulated by RelB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.
Martin
Ela
E
Centre for Immunology and Cancer Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.
O'Sullivan
Brendan
B
Low
Pauline
P
Thomas
Ranjeny
R
D000818:Animals; D000941:Antigens; D001327:Autoimmune Diseases / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006433:Hemocyanins; D007108:Immune Tolerance; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D000941:Antigens; D019013:CD40 Antigens; D011518:Proto-Oncogene Proteins; C497594:Relb protein, mouse; D014157:Transcription Factors; D016753:Interleukin-10; D051841:Transcription Factor RelB; D007371:Interferon-gamma; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin