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Modeling human adaptive immune responses with tonsil organoids.
Wagar, Lisa E; Salahudeen, Ameen; Constantz, Christian M; Wendel, Ben S; Lyons, Michael M; Mallajosyula, Vamsee; Jatt, Lauren P; Adamska, Julia Z; Blum, Lisa K; Gupta, Neha; Jackson, Katherine J L; Yang, Fan; Röltgen, Katharina; Roskin, Krishna M; Blaine, Kelly M; Meister, Kara D; Ahmad, Iram N; Cortese, Mario; Dora, Emery G; Tucker, Sean N; Sperling, Anne I; Jain, Aarti; Davies, D Huw; Felgner, Philip L; Hammer, Gregory B; Kim, Peter S; Robinson, William H; Boyd, Scott D; Kuo, Calvin J; Davis, Mark M.
Afiliação
  • Wagar LE; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  • Salahudeen A; Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Constantz CM; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
  • Wendel BS; Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
  • Lyons MM; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Mallajosyula V; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  • Jatt LP; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
  • Adamska JZ; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Blum LK; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Gupta N; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
  • Jackson KJL; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Yang F; Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
  • Röltgen K; Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA.
  • Roskin KM; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  • Blaine KM; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Meister KD; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Ahmad IN; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Cortese M; Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • Dora EG; Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Tucker SN; Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Sperling AI; Aerodigestive and Airway Reconstruction Center, Lucile Packard Children's Hospital, Stanford, CA, USA.
  • Jain A; Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Davies DH; Vaxart, South San Francisco, CA, USA.
  • Felgner PL; Vaxart, South San Francisco, CA, USA.
  • Hammer GB; Vaxart, South San Francisco, CA, USA.
  • Kim PS; Department of Medicine, University of Chicago, Chicago, IL, USA.
  • Robinson WH; Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Boyd SD; Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Kuo CJ; Vaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
  • Davis MM; Departments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Nat Med ; 27(1): 125-135, 2021 01.
Article em En | MEDLINE | ID: mdl-33432170
ABSTRACT
Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tonsila Palatina / Vacinas contra Influenza Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tonsila Palatina / Vacinas contra Influenza Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos