Context-dependent regulation of follicular helper T cell survival

Follicular helper T (T-FH) cells are a specialized subset of CD4(+) T cells that support germinal centers in producing high-affinity antibody-secreting and memory B cells in mammals and birds. Therefore, mechanisms have evolved to control the life and death of T-FH cells for balanced humoral immunity. Recent studies have collectively revealed at least two programmed cell death pathways, ferroptosis and pyroptosis, which govern T-FH cell survival under diverse physiopathological conditions including immunization, infection, gut homeostasis, and autoimmunity. We review major recent advances in our understanding of the context-dependent regulation of T-FH cell survival via cell death pathways that are closely connected with cellular metabolism. Such knowledge might be applied to inform new strategies aimed at modulating humoral immunity, potentially including enhancement of vaccine efficacies.

Automated summary

This article reviews recent advances in understanding the regulation of T-FH cell survival through cell death pathways that are closely connected with cellular metabolism. Such knowledge can be applied to guide strategies for modulating humoral immunity, including enhancing vaccine efficacy.