Why aging T cells fail: implications for vaccination

Abstract

The decline in CD4+ T cell function with aging contributes to reduced vaccine efficacy. In this commentary, we discuss the factors leading to age-related changes in T cell function and propose how they may be overcome to enhance vaccine efficacy for the elderly.

Figure 1

Genesis of Aging Defects We speculate that as CD4⁺ T cells develop and differentiate, they develop defects in responsiveness and function that accumulate and intensify with time, as indicated. These can be divided into “developmental” defects and “postthymic acquired defects,” as shown. Some extrinsic factors, acting at various stages of T cell development, are postulated to have negative effects, including exposure to oxidative and other stress, limitations of survival factors, thymic atrophy, and intrinsic factors such as increased age of the individual cells and their repeated homeostatic division. These are indicated in the red box, and we suggest they combine to undermine functionality. Stromal factors in bone marrow and thymus may act to preserve function. Whereas some defects may be irreversible, others can be reversed or muted by increasing extrinsic positive factors such as survival and inflammatory cytokines, as indicated by the blue box.