Abstract
BackgroundA reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses. In this study we compared the individual and polyfunctional expression of IFN-γ, MIP-1α, TNF-α, perforin, and IL-2 by T cell subsets, including the newly described stem cell like memory T cells (TSCM), in response to stimulation with superantigen staphylococcal enterotoxin B (SEB) in older (median age 80, n = 23) versus younger (median age 27; n = 23) adults.ResultsOlder age was associated with a markedly lower frequency of CD8+ naïve T cells (11% vs. 47%; p < 0.0001) and an expansion in memory T cell subsets including central memory (p < 0.05), effector memory and effector T cells (p < 0.001 for both). There was also a decline in CD4+ naïve T cells in older subjects (33% vs. 45%; p = 0.02). There were no differences in frequencies or polyfunctional profiles of TSCM between groups. CD8+ naïve cells in the older group had increased expression of all functional parameters measured compared to the younger subjects and exhibited greater polyfunctionality (p = 0.04). CD4+ naïve T cells in the older group also showed greater polyfunctionality with a TNF-α and IL-2 predominance (p = 0.005). CD8+ effector memory and effector T cells exhibited increased polyfunctionality in the older group compared with younger (p = 0.01 and p = 0.003).ConclusionsThese data suggest that aging does not have a negative effect on polyfunctionality and therefore this is likely not a major contributor to the immunesenescence described with aging.
Highlights
A reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses
We have previously demonstrated that age does not impact the polyfunctionality of memory CD8+ T cells in response to acute and chronic viral infections [17]
Age associated decline in naïve T cells with increased expression of functional parameters First we compared T cell subset frequencies between younger and older groups
Summary
A reduced number of naïve T cells along with an accumulation of differentiated cell types in aging have been described but little is known about the polyfunctionality of the T cell responses. Impaired cell-mediated immunity in older adults renders them increasingly susceptible to infectious diseases while at the same time leading to diminished immune responses following vaccination, the very strategy used to prevent infections [3,4]. In part immunesenescence is related to the changing phenotypic composition of T cells with age. The focus of studies on cell-mediated immunity in aging has been either on antigen specific vaccine or viral responses. Studies have demonstrated diminished expression of IFN-γ and granzyme B in CD8+ T-cell subsets in older adults vaccinated with influenza [10]. Diminished age related T cell responses to immunization with hepatitis B surface antigen have previously been demonstrated [11]. Similar studies with regards to viral specific T cell immunity such as RSV-specific responses have been reported to be deficient in older age [12,13]. There exists a paucity of data with regard to polyfunctional capabilities of T cells in aging and how it relates to the changing phenotype
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