Abstract

Reduced number of naïve T cells along with an accumulation of differentiated cell types in aging has been described but little is known about the polyfunctionality of T cells. In this study we compared the individual cytokine and polyfunctional profiles of T cell subsets, including newly described stem cell like memory T cells (TSCM) in response to stimulation with submaximal concentration of non-specific mitogen in older (median age 80, n=23) versus younger (median age 27; n=23) adults using multicolor flow cytometry. Secretion of IFN-γ, MIP-1α, TNF-α, perforin, and IL-2 were measured. Polyfunctionality was determined using FlowJo and SPICE (NIAID). Aging was associated with a marked decline in CD8+ naïve cells (11% vs. 47 %; p<0.0001) and an expansion in memory cell types including central memory (p<0.05), effector memory and effectors (p<0.001 for both) compared to younger subjects. There was also a decline in CD4+ naïve cells with age (33% vs. 45%; p=0.02). There were no differences in frequencies or cytokine profiles of TSCM between groups. CD8+ naïve cells in the older group had increased secretion of all cytokines measured compared to the younger subjects and exhibited greater polyfunctionality (p=0.03). CD4+ naïve cells among the older group also had greater polyfunctionality with a TNF-α and IL-2 dominance (p=0.001). The decline in naïve T cells in aging, rather than their polyfunctional potential maybe contributing to immunosenescence.

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