학술논문

Modeling human adaptive immune responses with tonsil organoids
Document Type
article
Source
Nature Medicine. 27(1)
Subject
Medical Microbiology
Biomedical and Clinical Sciences
Immunology
Infectious Diseases
Biotechnology
Pneumonia & Influenza
Vaccine Related
Prevention
Influenza
Emerging Infectious Diseases
Biodefense
Immunization
Underpinning research
1.1 Normal biological development and functioning
Prevention of disease and conditions
and promotion of well-being
3.4 Vaccines
Inflammatory and immune system
Infection
Good Health and Well Being
Adjuvants
Immunologic
B-Lymphocytes
COVID-19 Vaccines
Germinal Center
Hemagglutinin Glycoproteins
Influenza Virus
Humans
In Vitro Techniques
Influenza Vaccines
Lymphoid Tissue
Measles-Mumps-Rubella Vaccine
Organoids
Palatine Tonsil
Rabies Vaccines
T-Lymphocytes
Medical and Health Sciences
Biomedical and clinical sciences
Health sciences
Language
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.