T Cell Senescence

The aging of the immune system, referred to as immunosenescence, is associated with a dramatic reduction in responsiveness as well as functional dysregulation. This deterioration of immune function with advancing age contributes to the increased incidence among the elderly of morbidity and mortality from infectious disease, and possibly autoimmunity and cancer. In mammals, the defense for fighting infectious agents is composed of the innate and adaptive immune systems. Macrophages, granulocytes, and natural killer cells are the major components of the innate system whereas T and B lymphocytes comprise the adaptive system. Although both compartments are affected, adaptive immunity is most susceptible to the deleterious effects of aging. Innate immunity functions immediately after birth and manifests little change throughout life. In contrast, adaptive immunity is immature at birth, peaks at puberty and progressively declines thereafter. Though marginal alterations in B lymphocytes are apparent, the dramatic decline in humoral and cell-mediated responses is predominantly the consequence of senescent T cells. The following review focuses on the aging effect on T cells as reflected in altered function, subset representation, development, lifespan and activation. Age-associated alterations in antigen presenting cells are also discussed since these cells are required for T cell activation and may impact T cell function.