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Thymic regulatory T cells arise via two distinct developmental programs.
Owen, David L; Mahmud, Shawn A; Sjaastad, Louisa E; Williams, Jason B; Spanier, Justin A; Simeonov, Dimitre R; Ruscher, Roland; Huang, Weishan; Proekt, Irina; Miller, Corey N; Hekim, Can; Jeschke, Jonathan C; Aggarwal, Praful; Broeckel, Ulrich; LaRue, Rebecca S; Henzler, Christine M; Alegre, Maria-Luisa; Anderson, Mark S; August, Avery; Marson, Alexander; Zheng, Ye; Williams, Calvin B; Farrar, Michael A.
Afiliación
  • Owen DL; Center for Immunology, Masonic Cancer Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
  • Mahmud SA; Center for Immunology, Masonic Cancer Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
  • Sjaastad LE; Center for Immunology, Masonic Cancer Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
  • Williams JB; Section of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Spanier JA; Center for Immunology, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Simeonov DR; Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
  • Ruscher R; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
  • Huang W; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA, USA.
  • Proekt I; Center for Immunology, Masonic Cancer Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
  • Miller CN; Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
  • Hekim C; Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA.
  • Jeschke JC; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
  • Aggarwal P; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
  • Broeckel U; Center for Immunology, Masonic Cancer Center, and the Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
  • LaRue RS; Section of Rheumatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Henzler CM; Section of Genomic Pediatrics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Alegre ML; Section of Genomic Pediatrics, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
  • Anderson MS; Supercomputing Institute for Advanced Computational Research, University of Minnesota, Minneapolis, MN, USA.
  • August A; Supercomputing Institute for Advanced Computational Research, University of Minnesota, Minneapolis, MN, USA.
  • Marson A; Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Zheng Y; Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
  • Williams CB; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
  • Farrar MA; Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Nat Immunol ; 20(2): 195-205, 2019 02.
Article en En | MEDLINE | ID: mdl-30643267
ABSTRACT
The developmental programs that generate a broad repertoire of regulatory T cells (Treg cells) able to respond to both self antigens and non-self antigens remain unclear. Here we found that mature Treg cells were generated through two distinct developmental programs involving CD25+ Treg cell progenitors (CD25+ TregP cells) and Foxp3lo Treg cell progenitors (Foxp3lo TregP cells). CD25+ TregP cells showed higher rates of apoptosis and interacted with thymic self antigens with higher affinity than did Foxp3lo TregP cells, and had a T cell antigen receptor repertoire and transcriptome distinct from that of Foxp3lo TregP cells. The development of both CD25+ TregP cells and Foxp3lo TregP cells was controlled by distinct signaling pathways and enhancers. Transcriptomics and histocytometric data suggested that CD25+ TregP cells and Foxp3lo TregP cells arose by coopting negative-selection programs and positive-selection programs, respectively. Treg cells derived from CD25+ TregP cells, but not those derived from Foxp3lo TregP cells, prevented experimental autoimmune encephalitis. Our findings indicate that Treg cells arise through two distinct developmental programs that are both required for a comprehensive Treg cell repertoire capable of establishing immunotolerance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Timo / Diferenciación Celular / Linfocitos T Reguladores / Encefalomielitis Autoinmune Experimental / Células Progenitoras Linfoides Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Timo / Diferenciación Celular / Linfocitos T Reguladores / Encefalomielitis Autoinmune Experimental / Células Progenitoras Linfoides Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos