Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.
Toll-like receptors (TLRs) control activation of adaptive immune responses by antigen-presenting cells (APCs). However, initiation of adaptive immune responses is also controlled by regulatory T cells (TR cells), which act to prevent activation of autoreactive T cells. Here we describe a second mechanism of immune induction by TLRs, which is independent of effects on costimulation. Microbial induction of the Toll pathway blocked the suppressive effect of CD4+CD25+ TR cells, allowing activation of pathogen-specific adaptive immune responses. This block of suppressor activity was dependent in part on interleukin-6, which was induced by TLRs upon recognition of microbial products.
Pasare
Chandrashekhar
C
Howard Hughes Medical Institute and Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Medzhitov
Ruslan
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000276:immunology; D029721:Drosophila Proteins; D007108:Immune Tolerance; D007114:Immunization; D015850:Interleukin-6 / Q000378:metabolism / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88; D010047:Ovalbumin / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000378:metabolism; D017634:Self Tolerance; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000943:Antigens, Differentiation; D017077:Culture Media, Conditioned; D015226:Dinucleoside Phosphates; D029721:Drosophila Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D010047:Ovalbumin; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; C507780:Myd88 protein, mouse; C015772:CpG dinucleotide