T cell fate decisions during memory cell generation with aging
Seminars in immunology, 2023•Elsevier
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 …
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 …
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.
Elsevier