Effects of aging on human leukocytes (part I): immunophenotyping of innate immune cells.

Immunosenescence is a hallmark of the aging immune system, leading to increased susceptibility to infections in the aged population and decreased ability to eradicate infectious pathogens. These effects, in turn, result in an increased burden on the healthcare system due to elevated frequency and duration of hospital visits. Growing evidence suggests that cells of the innate immune system are central modulators for the initiation and maintenance of an adequate pathogen-specific response through the adaptive immune system. While there are many reports on age-dependent alterations and dysfunctions of the adaptive immune system, the underlying mechanisms and effects of natural aging on the composition of the innate immune system remain unknown. Here, we present the results obtained from the comprehensive immunophenotyping of innate leukocyte populations, examined for age-related alterations within different sub-populations assessed using multi-parametric flow cytometry. We compared peripheral blood mononuclear cells from 24 young (aged 19-30 years) and 26 elderly (aged 53-67 years) donors. For classical CD16(+)CD56(dim) NK cells, the fraction of CD62L(+)CD57(+) was diminished in the elderly donors compared with young individuals, while the other investigated NK subsets remained unaffected by age. Both transitional monocytes and non-classical CD14(+-)CD16(++) monocytes were increased in the elderly compared with the young. The populations of pDCs and mDC2 were decreased among the elderly. These data demonstrate that the dynamics of the mDC subsets might counteract decreased virus surveillance. Furthermore, these data show that the maturation of NK cells might gradually slow down.

Effects of aging on human leukocytes (part II): immunophenotyping of adaptive immune B and T cell subsets.

Immunosenescence results from a continuous deterioration of immune responses resulting in a decreased response to vaccines. A well-described age-related alteration of the immune system is the decrease of de novo generation of T and B cells. In addition, the accumulation of memory cells and loss of diversity in antigen specificities resulting from a lifetime of exposure to pathogens has also been described. However, the effect of aging on subsets of γδTCR(+) T cells and Tregs has been poorly described, and the efficacy of the recall response to common persistent infections in the elderly remains obscure. Here, we investigated alterations in the subpopulations of the B and T cells among 24 healthy young (aged 19-30) and 26 healthy elderly (aged 53-67) individuals. The analysis was performed by flow cytometry using freshly collected peripheral blood. γδTCR(+) T cells were overall decreased, while CD4(+)CD8(-) cells among γδTCR(+) T cells were increased in the elderly. Helios(+)Foxp3(+) and Helios(-)Foxp3(+) Treg cells were unaffected with age. Recent thymic emigrants, based on CD31 expression, were decreased among the Helios(+)Foxp3(+), but not the Helios(-)Foxp3(+) cell populations. We observed a decrease in Adenovirus-specific CD4(+) and CD8(+) T cells and an increase in CMV-specific CD4(+) T cells in the elderly. Similarly, INFγ(+)TNFα(+) double-positive cells were decreased among activated T cells after Adenovirus stimulation but increased after CMV stimulation. The data presented here indicate that γδTCR(+) T cells might stabilize B cells, and functional senescence might dominate at higher ages than those studied here.