Dysfunctional peripheral T follicular helper cells dominate in people with impaired influenza vaccine responses: Results from the FLORAH study
| Autor: | Varghese K. George, Li Pan, Suresh Pallikkuth, Lesley R. de Armas, Savita Pahwa, Rajendra Pahwa, Kristopher L. Arheart, Stefano Rinaldi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male RNA viruses Viral Diseases B Cells Physiology HIV Infections Antibodies Viral Lymphocyte Activation Interleukin 21 White Blood Cells 0302 clinical medicine Influenza A Virus H1N1 Subtype Immunodeficiency Viruses Animal Cells Immune Physiology Medicine and Health Sciences Public and Occupational Health Biology (General) Antigens Viral Pathology and laboratory medicine B-Lymphocytes Innate Immune System Vaccines biology General Neuroscience Vaccination H1N1 T-Lymphocytes Helper-Inducer Medical microbiology Vaccination and Immunization 3. Good health medicine.anatomical_structure Phenotype Infectious Diseases Influenza Vaccines Influenza A virus Viruses Cytokines Female Inflammation Mediators Pathogens Cellular Types General Agricultural and Biological Sciences Research Article Adult Infectious Disease Control Influenza vaccine QH301-705.5 Immune Cells Immunology Antigen-Presenting Cells Microbiology General Biochemistry Genetics and Molecular Biology Inducible T-Cell Co-Stimulator Protein 03 medical and health sciences Young Adult Antigen Neutralization Tests Influenza Human Retroviruses medicine Humans Influenza viruses Lymphocyte Count Antigen-presenting cell Antibody-Producing Cells B cell Cell Proliferation CD40 Blood Cells General Immunology and Microbiology Cluster of differentiation Tumor Necrosis Factor-alpha Interleukins Lentivirus Organisms Viral pathogens Germinal center Biology and Life Sciences HIV Cell Biology Molecular Development Influenza Microbial pathogens 030104 developmental biology Immune System biology.protein Interleukin-2 Preventive Medicine 030217 neurology & neurosurgery Developmental Biology Orthomyxoviruses |
| Zdroj: | PLoS Biology PLoS Biology, Vol 17, Iss 5, p e3000257 (2019) |
| ISSN: | 1545-7885 |
| Popis: | Antigen-primed cluster of differentiation (CD) 4+ T follicular helper (Tfh) cells interact with B cells in the germinal centers (GCs) of lymph nodes to generate vaccine-induced antibody (Ab) responses. In the circulation, peripheral Tfh (pTfh) cells, a subset of memory CD4 T cells, serve as surrogates for GC Tfh because of several functional and phenotypic similarities between them. We investigated features of H1N1 influenza antigen-specific pTfh (Ag.pTfh) in virologically controlled HIV+ volunteers on antiretroviral therapy (ART) and healthy control (HC) participants selected from a seasonal influenza vaccine responsiveness study. Selection of the participants was made based on age, defined as young (18–40 y) and old (>60 y) and on their classification as a vaccine responder (VR) or vaccine nonresponder (VNR). VRs demonstrated expansion of CD40L+ and CD69+ Ag.pTfh, with induction of intracellular interleukin 21 (IL-21) and inducible costimulator (ICOS) post vaccination; these responses were strongest in young HC VRs and were less prominent in HIV+ individuals of all ages. Ag.pTfh in VNRs exhibited dramatically different characteristics from VRs, displaying an altered phenotype and a cytokine profile dominated by cytokines IL-2, tumor necrosis factor alpha (TNF-α), or IL-17 but lacking in IL-21. In coculture experiments, sorted pTfh did not support the B cell IgG production in VNRs and were predominantly an inflammatory T helper 1 (Th1)/T helper 17 (Th17) phenotype with lower ICOS and higher programmed cell death protein 1 (PD1) expression. Induction of IL-21 and ICOS on Ag.pTfh cells are negatively affected by both aging and HIV infection. Our findings demonstrate that dysfunctional Ag.pTfh cells with an altered IL-21/IL-2 axis contribute to inadequate vaccine responses. Approaches for targeting inflammation or expanding functional Tfh may improve vaccine responses in healthy aging and those aging with HIV infection. This study identifies qualities of flu vaccine-specific T follicular helper cells that are important for vaccine responses, and delineates deficiencies that are associated with impaired vaccine responses in biologic aging and HIV infection in humans. |
| Databáze: | OpenAIRE |
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