Changes of T-cell Immunity Over a Lifetime

Abstract

T-cell immunity undergoes a complex and continuous remodeling with aging. Understanding those dynamics is essential in refining immunosuppression. Aging is linked to phenotypic and metabolic changes in T-cell immunity, many resulting into impaired function and compromised effectiveness. Those changes may impact clinical immunosuppression with evidences suggesting age-specific efficacies of some (CNI and mammalian target of rapamycin inhibitors) but not necessarily all immunosuppressants. Metabolic changes of T cells with aging have only recently been appreciated and may provide novel ways of immunosuppression. Here, we provide an update on changes of T-cell immunity in aging.

Figure 1:

Changes in cellular metabolism of senescent T cells. In activated senescent T cells, ATP production is impaired due to altered glycolytic flux and compromised mitochondrial respiration. Though old T cells have higher mtROS leakage, enhanced pentose phosphate pathway results in a burst of reductive molecule and clearance of mtROS. NFAT and NF-κB fail to translocate into nuclear because of altered cellular redox state. Consequently, the production of IL-2 is impaired.

Figure 2:

T cell aging is characterized by changes in phenotype, alterations in cellular metabolism and impaired function. These alterations contribute at least partially to the clinic phenotype.