FOXO1 constrains activation and regulates senescence in CD8 T cells

Naive and memory T cells are maintained in a quiescent state, yet capable of rapid response and differentiation to antigen challenge via molecular mechanisms that are not fully understood. In naive cells, the deletion of Foxo1 following thymic development results in the increased expression of multiple AP-1 family members, rendering T cells less able to respond to antigenic challenge. Similarly, in the absence of FOXO1, post-infection memory T cells exhibit the characteristics of extended activation and senescence. Age-based analysis of human peripheral T cells reveals that levels of FOXO1 and its downstream target, TCF7, are inversely related to host age, whereas the opposite is found for AP-1 factors. These characteristics of aging also correlate with the formation of T cells manifesting features of cellular senescence. Our work illustrates a role for FOXO1 in the active maintenance of stem-like properties in T cells at the timescales of acute infection and organismal life span.

Automated summary

This study demonstrates the crucial role of FOXO1 in maintaining cellular vitality and response to antigenic stress in T cells. Different cellular age states may lead to alterations in levels of FOXO1, TCF7, and AP-1 factors. These characteristics are also associated with the formation of T cells with features of cellular senescence.