T cell ageing: effects of age on development, survival & function

Abstract

Age associated decline of the immune system continues to be a major health concern. All components of innate and adaptive immunity are adversely affected to lesser or greater extent by ageing resulting in an overall decline of immunocompetence. As a result in the aged population, there is increased susceptibility to infection, poor responses to vaccination, and increased incidence of autoreactivity. There is an increasing focus on the role of T cells during ageing because of their impact on the overall immune responses. A steady decline in the production of fresh naïve T cells, more restricted T cell receptor (TCR) repertoire and weak activation of T cells are some of the effects of ageing. In this review we summarize our present understanding of the effects of ageing on naïve CD4 T cells and potential approaches for therapeutic interventions to restore protective immunity in the aged population.

Fig

Effect of ageing on adaptive immunity. (A) Broad outline of the adaptive immune responses in the young host. Antigen presenting cells (APCs) pick up invading organisms by phagocytosis and migrate to regional lymph nodes. Here they encounter diverse population of naïve T cells which are produced continuously by a well-functioning thymus. On encounter with the antigen presented as peptide major histocompatibility complex (pMHC) complex by professional APCs such as dendritic cells (DCs), T cells get activated and multiply. The expanded population further differentiates into the effector and memory T cells. Naïve B cells are also generated steadily by the bone marrow in the young. On encounter with antigen these get activated and differentiate to produce memory B cells and antibody secreting plasma cells. In the germinal centre antigen-specific T cells provide help to B cells for class switching. (B) Broad outline of the adaptive immune responses in the aged host. As compared to the young hosts, efficiency of APC migration and making stable contact with T cells (immunological synapse) decreases. This results in qualitatively and quantitatively poor activation and differentiation of T cells. The thymic output also decreases in the aged host further compromising the immune response. B cell output from the bone marrow is also adversely affected with age. T-B interactions happen less efficiently with fewer germinal centres (ac) getting formed and poor differentiation process leading to poor antibody responses. The red crosses indicate a reduction in the respective activity.