How Aging Affects T Lymphocyte-Mediated Immunity

age-dependent decline in immune responses while autoimmune diseases increase in incidence. The authors hypothesize that the same defects that account for the decreased ability to generate protective immune responses also contribute to the increased risk of autoimmunity. The major risk factor for autoimmunity in old age appears to be the reshaping of the peripheral T cell receptor repertoire, which is driven by the age-dependent involution of the thymus. The consequent increase in homeostatic T cell proliferation prolongs peripheral T cell survival and selects for self antigen and cytokine responsiveness, thereby facilitating the generation of autoreactive T cells. Fulop et al. (7) review longitudinal studies that analyzed immune parameters predictive of survival. These studies defined an immune risk profile and showed that persistent viral infections, in particular Cytomegalovirus infection, can accelerate human T cell aging. In an opinion article, Aspinall and Lang (8) focus on the impact of influenza virus infection in the elderly and highlight the current problems of designing a more effective vaccine for people older than 60 years of age. The authors propose a portfolio approach and emphasize that future developments should move toward a more personalized treatment regimen that may even be combined with therapeutic approaches that target immune aging itself. In another opinion article, Flavell and colleagues (9) accentuate the need to define a robust set of markers of T cell aging. The authors summarize our current knowledge about markers of T cell aging and emphasize the lack of data about T cell phenotypes and functions in various human organs and tissues, which would be important to better understand the fate of different T cell types and the role of specific markers. Eventually, the identification of a set of markers for immunosenescence would be a valuable clinical tool and would allow to evaluate potential therapeutic interventions aiming to prevent or reverse immune cell aging, and to personalize vaccination strategies for elderly people at risk, thereby increasing life and health span.