The impact of senescence-associated T cells on immunosenescence and age-related disorders

Immunosenescenceis age-associated changes in the immunological functions, including diminished acquired immunity against infection, pro-inflammatory traits, and increased risk of autoimmunity. The proportions of memory-phenotype T cellsin the peripheral T cellpopulation steadily increase with age, but the relationship between this change and immunosenescentphenotypes remains elusive. Recently, we identified a minor memory-phenotype CD4+ T cellsubpopulation that constitutively expressed PD-1 and CD153 as a bona fideage-dependent T cellpopulation; we termed these cells senescence-associated T (SA- T) cells. SA- T cellsexhibit characteristic features of cellular senescence, with defective T cell receptor-mediated proliferation and T cellcytokine production. However, upon T cell receptorstimulation, SA- T cellssecrete abundant atypical pro-inflammatory cytokines such as osteopontinand chemokines, reminiscent of the SA-secretory phenotype. In addition to aging, SA- T cellsaccumulate and cause persistent inflammation in tissues following a wide range of insults including immune complex deposition, metabolic stresses, vascular damages, and tumors. In this review, we summarize the recent understanding of immunosenescencewith particular focus on SA- T cellsand their role in various age-related disorders.