Impaired HA-specific T follicular helper cell and antibody responses to influenza vaccination are linked to inflammation in humans
Autor: | Carly E. Whyte, James Dooley, Michelle A. Linterman, James Lee, Jia Le Lee, Martin S. Zand, Silvia Innocentin, Jiong Wang, Edward J. Carr, Danika L. Hill, William W. Kwok, Eddie A. James, Adrian Liston |
---|---|
Přispěvatelé: | Hill, Danika L [0000-0001-6284-7061], Carr, Edward J [0000-0001-9343-4593], Linterman, Michelle [0000-0001-6047-1996], Apollo - University of Cambridge Repository, Linterman, Michelle A [0000-0001-6047-1996] |
Rok vydání: | 2021 |
Předmět: |
Mouse
QH301-705.5 T cell Science Cell Inflammation Major histocompatibility complex General Biochemistry Genetics and Molecular Biology t follicular helper cells Flow cytometry immunology 03 medical and health sciences 0302 clinical medicine Immunology and Inflammation medicine Humans antibodies Biology (General) 030304 developmental biology 0303 health sciences General Immunology and Microbiology biology medicine.diagnostic_test General Neuroscience T-cell receptor Vaccination General Medicine vaccines 3. Good health medicine.anatomical_structure Hemagglutinins Influenza Vaccines ageing Immunology Antibody Formation biology.protein Medicine medicine.symptom Antibody influenza germinal centre 030215 immunology Research Article Human |
Zdroj: | eLife, Vol 10 (2021) eLife |
Popis: | Antibody production following vaccination can provide protective immunity to subsequent infection by pathogens such as influenza viruses. However, circumstances where antibody formation is impaired after vaccination, such as in older people, require us to better understand the cellular and molecular mechanisms that underpin successful vaccination in order to improve vaccine design for at-risk groups. Here, by studying the breadth of anti-haemagglutinin (HA) IgG, serum cytokines, and B and T cell responses by flow cytometry before and after influenza vaccination, we show that formation of circulating T follicular helper (cTfh) cells was associated with high-titre antibody responses. Using Major Histocompatability Complex (MHC) class II tetramers, we demonstrate that HA-specific cTfh cells can derive from pre-existing memory CD4+T cells and have a diverse T cell receptor (TCR) repertoire. In older people, the differentiation of HA-specific cells into cTfh cells was impaired. This age-dependent defect in cTfh cell formation was not due to a contraction of the TCR repertoire, but rather was linked with an increased inflammatory gene signature in cTfh cells. Together, this suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people. |
Databáze: | OpenAIRE |
Externí odkaz: |