T Cell Fate Decisions During Memory Cell Generation With Aging

Authors

Ines Sturmlechner
Abhinav Jain
Yunmei Mu
Cornelia M Weyand
Jörg J Goronzy

Publication Date

9-1-2023

Journal

Seminars in Immunology

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.

Keywords

T cell memory, T cell ageing, T cell differentiation, inflammageing, mTORC1, TCF1

Comments

PMID: 37494738