T cell function in the aged: Lessons learned from animal models

The deterioration of immune function with advancing age contributes to the increased incidence of morbidity and mortality among the elderly from infectious disease and possibly cancer. The innate and adaptive arms of immunity are affected by the deleterious effects of aging, but it is adaptive immunity, and in particular T lymphocytes, that is most susceptible to these effects. The aging of the immune system, referred to as immunosenescence, is associated with a dramatic decline in responsiveness as well as functional dysregulation. Age-associated alterations in T cells are evident at all stages of its development, and it is these changes that contribute to the overall increased susceptibility to infection and possibly cancer. Although there is an enormous effort worldwide to develop vaccines, much of the research is performed with young animals. Because the immune system of the aged is different from that of the young, many of the findings cannot be extrapolated. In this review, we will discuss those differences in T cell immunity of the aged, relate how these differences influence the immune response of the aged to pathogens as well as to tumors, and describe the current approaches to rejuvenate the aged immune response. Although the majority of the conclusions on T cell immunity in the aged are based on studies in the murine model, many of these findings can be extended to the human model. Throughout this review, we have noted those findings that are specific to humans.