Accumulation of immune-suppressive CD4 + T cells in aging – tempering inflammaging at the expense of immunity

The 'immune risk profile' has been shown to predict mortality in the elderly, highlighting the need to better understand age-related immune dysfunction. While aging leads to many defects affecting all arms of the immune system, this review is focused on the accrual of immuno-suppressive CD4 + T cell populations, including FoxP3 + regulatory T cells, and subsets of IL-10-producing T follicular helper cells. New data suggest that such accumulations constitute feedback mechanisms to temper the ongoing progressive low-grade inflammation that develops with age, the so-called "inflammaging", and by doing so, how they have the potential to promote healthier aging. However, they also impair effector immune responses, notably to infections, or vaccines. These studies also reinforce the idea that the aged immune system should not be considered as a poorly functional version of the young one, but more as a dynamic system in which CD4 + T cells, and other immune/non-immune subsets, differentiate, interact with their milieu and function differently than in young hosts. A better understanding of these unique interactions is thus needed to improve effector immune responses in the elderly, while keeping inflammaging under control.