title: Conditioning of naive CD4(+) T cells for enhanced peripheral Foxp3 induction by nonspecific bystander inflammation.
abstract: Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines affect the immune system in a context-dependent manner. Here we show that nonspecific bystander inflammation conditions naive CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation. This results in inhibition of immune responses in vivo via a Foxp3-dependent effect on antigen-specific naive CD4(+) T cell precursors. Such conditioning may have evolved to allow immunity to infection while limiting subsequent autoimmunity caused by release of self-antigens in the wake of infection. Furthermore, this phenomenon suggests a mechanistic explanation for the idea that early tuning of the immune system by infection affects the long-term quality of immune regulation.
authors.affiliation: Benaroya Research Institute, Immunology Research Program, Seattle, Washington, USA.
authors.forename: Lucas J
authors.initials: LJ
authors.lastname: Thompson
authors.affiliation: Benaroya Research Institute, Immunology Research Program, Seattle, Washington, USA.
authors.forename: Jen-Feng
authors.initials: JF
authors.lastname: Lai
authors.affiliation: Benaroya Research Institute, Immunology Research Program, Seattle, Washington, USA.|Department of Immunology, University of Washington, Seattle, Washington, USA.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Valladao
authors.affiliation: Benaroya Research Institute, Immunology Research Program, Seattle, Washington, USA.|Department of Immunology, University of Washington, Seattle, Washington, USA.
authors.forename: Tennille D
authors.initials: TD
authors.lastname: Thelen
authors.affiliation: Kings College London, London, UK.
authors.forename: Zoe L
authors.initials: ZL
authors.lastname: Urry
authors.affiliation: Benaroya Research Institute, Immunology Research Program, Seattle, Washington, USA.
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology*; D001324:Autoantigens; D015551:Autoimmunity / Q000276:immunology*; D024201:Bystander Effect / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000187:drug effects / Q000276:immunology* / Q000494:pharmacology; D019175:DNA Methylation; D003920:Diabetes Mellitus / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D007249:Inflammation; D007369:Interferon Inducers / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061166:Peripheral Tolerance / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017634:Self Tolerance / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D001324:Autoantigens; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007369:Interferon Inducers; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse