There are various approaches to improve immune responses with age. First, there are vaccine approaches to protect older people from infection. One strategy is to use adjuvants. Adjuvants increase the ability of APCs to prime antigen specific T cells, partly, by stimulating innate receptors such as TLRs. For example, Poly I:C (a TLR3 agonist) is shown to be effective in enhancing the CD4+
T cell help in aged mice [44
], although this approach has yet to be applied to protection from viral infection.
Aging induces thymic involution leading to reduced production of naïve T-cells. Hence, strategies to prevent thymic atrophy with age or increasing T-cell output hold potential in counteracting the impact of age on the immune system. Administration of thymic growth factors including keratinocyte growth factor (KGF), IL-7 and ghrelin may increase thymic output to counter the effects of aging on thymic involution. KGF acts by enhancing IL-7 production within the thymus, by binding to KGF receptors on thymic epithelial cells [45
]. IL-7 increases thymic output of T-cells allowing for the maintenance of long-lived memory T cells, following vaccination [47
]. Hence, there may be pharmacological approaches to counter age-induced thymic atrophy, which may improve T cell memory responses and increase vaccine efficacy in older people.
Another promising strategy is to prevent age-induced telomere shorting with age. This approach is based on the observation that telomere shortening with aging is associated with overall decreased replicative potential and function of T lymphocytes. Telomerase activation elongates telomere and is associated with T cell activation, which could increase the ability of the cell to divide. For example, treatment of CD8+
T cells from HIV-infected individuals with TAT-2 (a small molecular telomerase activator) has the dual effects of increasing tolemerase activity as well as enhancement of a variety of antiviral effector functions including antigen specific cytotoxicity and IFN-γ production [48
]. This approach may prevent telomerase shortening with age and possibly improve anti-viral T-cell responses.