Quantitative Multiplexed Imaging Analysis Reveals a Strong Association between Immunogen-Specific B Cell Responses and Tonsillar Germinal Center Immune Dynamics in Children after Influenza Vaccination
| Autor: | Filippo Maria Tucci, Yiannis Dimopoulos, Constantinos Petrovas, Richard A. Koup, Rita De Vito, Paolo Rossi, Nicola Cotugno, Giulia Macchiarulo, Salvatore Rocca, Maria R. Castrucci, Sandeep Narpala, Donato Amodio, Adrian B. McDermott, Paolo Palma |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Helper-Inducer T-Lymphocytes Immunology Palatine Tonsil Antibodies Viral Antigens Viral B-Lymphocytes Biomarkers Child Cytokines Germinal Center Humans Immunophenotyping Influenza Vaccines Influenza Human Lymphocyte Count Phenotype T-Lymphocytes Helper-Inducer Vaccination Biology Article Settore MED/06 Antibodies 03 medical and health sciences 0302 clinical medicine Immune system Antigen stomatognathic system medicine Immunology and Allergy Viral CXCL13 Antigens B cell Settore MED/38 - Pediatria Generale e Specialistica Germinal center Settore MED/38 Influenza 030104 developmental biology medicine.anatomical_structure biology.protein Antibody 030215 immunology Human |
| Popis: | Generation of Ag-specific humoral responses requires the orchestrated development and function of highly specialized immune cells in secondary lymphoid organs. We used a multiparametric approach combining flow cytometry, confocal microscopy, and histocytometry to analyze, for the first time to our knowledge in children, tonsils from seasonal influenza–vaccinated children. We used these novel imaging assays to address the mucosal immune dynamics in tonsils investigating the spatial positioning, frequency, and phenotype of immune cells after vaccination. Vaccination was associated with a significantly higher frequency of follicular helper CD4 T cells compared with the unvaccinated control group. The imaging analysis revealed that potential suppressor (FOXP3hi) CD4 T cells are mainly located in extrafollicular areas. Furthermore, a significantly reduced frequency of both follicular and extrafollicular FOXP3hi CD4 T cells was found in the vaccine group compared with the control group. Levels of circulating CXCL13 were higher in those vaccinated compared with controls, mirroring an increased germinal center reactivity in the tonsils. Notably, a strong correlation was found between the frequency of tonsillar T follicular helper cells and tonsillar Ag-specific Ab-secreting cells. These data demonstrate that influenza vaccination promotes the prevalence of relevant immune cells in tonsillar follicles and support the use of tonsils as lymphoid sites for the study of germinal center reactions after vaccination in children. |
| Databáze: | OpenAIRE |
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