Aging and T-cell-mediated immunity

Changes in the T-lymphocyte compartment represent the most critical component of immunological aging. Recent studies have demonstrated that the age-related decline in T-cell-mediated immunity is a multifactorial phenomenon affecting T-cell subset composition as well as several proximal events such as protein tyrosine phosphorylation, generation of second messengers, calcium mobilization and translocation of protein kinase C, and distal events such as lymphocyte proliferation and cytokine production of the T-cell activation pathway. Age-related T-cell immune deficiency is preceded by thymic involution and is influenced by several intrinsic as well as extrinsic factors. Further, the role of monocytes and macrophages in T-cell activation changes with advancing age. This brief review will summarize the current knowledge of the cellular as well as molecular aspects of immunodeficiency of T cells due to aging, some of the paradoxes of aging as related to T-cell-mediated immunity, and possible factors which contribute to this paradox. Finally, experimental approaches will be suggested that might resolve these controversies and that might provide insights into the diverse and complex mechanisms that contribute to immunodeficiency of T cells. Ultimately these studies may suggest possible therapeutic interventions to enhance immune function in the elderly.