Impact of age on T cell signaling: a general defect or specific alterations?

Decreased immune responsiveness associated with aging is generally termed "immunosenescence". Several theories have been proposed to explain age-related declines in immune responses. Here, we will focus on and describe potential defects in T cell signal transduction from the membrane to the nucleus, leading to changes in the type, intensity and duration of the response as a major factor contributing to immunosenescence. We will first detail T cell signaling through the T cell receptor (TCR), CD28 and IL-2 receptor (IL-2R) and then discuss the observed age-related alterations to these signaling pathways. The role of membrane rafts in T cell signaling and T cell aging will be described. These factors will be considered in the context of the notion that age-related changes to T cell signaling may be attributed to changes in the functionality of the T cells due to shifts in T cell subpopulations with age. For this reason, we conclude by highlighting the application of multiparametric signaling analysis in leukocyte subsets using flow cytometry as a means to obtain a clearer picture with respect to age-related changes to immune signaling.