Age-related changes in CD8 T cell homeostasis and immunity to infection

Abstract

Studies of CD8 T cell responses to vaccination or infection with various pathogens in both animal models and human subjects have revealed a markedly consistent array of age-related defects. In general, recent work shows that aged CD8 T cell responses are decreased in magnitude, and show poor differentiation into effector cells, with a reduced arsenal of effector functions. Here we review potential mechanisms underlying these defects. We specifically address phenotypic and numeric changes to the naïve CD8 T cell precursor pool, the impact of persistent viral infection(s) and inflammation, and contributions of the aging environment in which these cells are activated.

Figure 1. Components that contribute to age-related impaired CD8 T cell responses

Figure depicts the features of the CD8 T cell immune response in adult (top) and old (bottom) mice, although several of the features have also been also found in humans (see Table 1). Note that the reduced naïve CD8 T cell pool (lower left corner, bottom panel) is faced with potentially reduced stimulation by old DC which can exhibit decreased uptake of Ag and impaired maturation; that and cell-intrinsic defects in proliferation and differentiation of old naïve CD8 T cells result in a reduced effector pool with insufficient effector function, which is evident both in the total pool and at an individual cell basis.