Abstract
The defense against infectious diseases, either through natural immunity or after vaccinations, relies on the generation and maintenance of protective T cell memory. Naïve T cells are at the center of memory T cell generation during primary responses. Upon activation, they undergo a complex, highly regulated differentiation process towards different functional states. Naïve T cells maintained into older age have undergone epigenetic adaptations that influence their fate decisions during differentiation. We review age-sensitive, molecular pathways and gene regulatory networks that bias naïve T cell differentiation towards effector cell generation at the expense of memory and Tfh cells. As a result, T cell differentiation in older adults is associated with release of bioactive waste products into the microenvironment, higher stress sensitivity as well as skewing towards pro-inflammatory signatures and shorter life spans. These maladaptations not only contribute to poor vaccine responses in older adults but also fuel a more inflammatory state.
Original language | English (US) |
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Article number | 101800 |
Journal | Seminars in immunology |
Volume | 69 |
DOIs | |
State | Published - Sep 2023 |
Keywords
- Inflammageing
- T cell ageing
- T cell differentiation
- T cell memory
- TCF1
- mTORC1
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology