Age-associated alteration in naive and memory Th17 cell response in humans

Abstract

Th17 cells produce IL-17 that plays an important role in host defense. However, little is known about whether aging affects human Th17 cells. Here we demonstrated that healthy elderly people (age≥65) had a decreased frequency of IL-17-producing cells in memory CD4+ T cells compared to healthy young people (age≤40) while both groups had similar frequencies of IFN-γ-producing cells in the same memory cell subset as measured by flow cytometry. In contrast, the healthy elderly had increased differentiation of IL-17-producing effector cells but not IFN-γ-producing cells from naïve CD4+ T cells compared to the healthy young. The results of ELISA also showed similar findings with increased IL-17 production from naïve CD4+ T cells and decreased IL-17 production from memory CD4+ T cells in the elderly compared to the young. These findings indicate that aging differentially affects naïve and memory Th17 cell responses in humans.

Aging disturbs the balance between effector and regulatory CD4+ T cells

“…Similar to previous studies, we observed that Th1, Th2 and Th17 cell numbers are either retained or decreased in the elderly (Alberti et al, 2006;Karanfilov et al, 1999;Lee et al, 2011). Both in young and aged individuals, these T eff subsets primarily resided within the memory CD4+ T cell compartment.…”

“…In the latter study, however, the number of Th17 cells may have been overestimated, as Th17 cells were solely identified by expression of the IL-23 receptor, which is also expressed by cells other than Th17 cells (Parham et al, 2002). We and others identified Th17 cells by expression of their hallmark cytokine IL-17 and found decreased numbers of these cells in elderly individuals (Lee et al, 2011). Our data therefore indicate that aging in healthy elderly substantially tilts the T reg /Th17 balance towards T reg cells.…”

“…IL-4 producing Th2 cells promote immune responses to parasites, whereas IL-17 producing Th17 cells are involved in protection against extracellular bacteria and yeasts. Various studies have shown that these subsets of effector T (T eff ) cells are either retained or decreased in the circulation of aged humans (Alberti et al, 2006;Karanfilov et al, 1999;Lee et al, 2011).…”

CD11c + Dendritic Cells Accelerate the Rejection of Older Cardiac Transplants via Interleukin-17A

“…Elevated frequencies of Th17 cells have been observed in old mice and humans 21,22 . More importantly, Th17 cells have been linked to critical pathways in allograft rejection 23 .…”

Simulating the Dynamics of T Cell Subsets throughout the Lifetime

“…One study concluded upon the oscillatory nature of T reg numbers through life, with peaks in adolescence and in over 60 year olds [8]. A recent study in T h 17 cells with age showed a small decrease in the frequency of T h 17 cells in the CD4 + memory population in elderly donors relative to young [9]. However, for the balance between T reg s and T h 17 cells, there is currently no published literature.…”