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

Abstract

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.

Fig. 1

Monocytes and DCs. Cells were gated as described in Supplementary Fig. 1. Shown are boxplots for frequencies and total cell numbers/microliter whole blood for a CD14⁺⁺CD16⁻ classical monocytes; b CD14⁺⁺CD16⁺ transitional monocytes; c CD14^+–CD16⁺⁺ non-classical monocytes; d non-monocytes; e pDC; f total mDC; g mDC1; h mDC2. The box indicates the 25th, 50th, and 75th percentiles; the whiskers the minimum and maximum values excluding outliers. Wilcoxon rank-sum test was used to test for differences and p values <0.05 are reported

Fig. 2

CD56^dim NK cells. Cells were gated as described in Supplementary Fig. 2. Shown are boxplots for frequencies and total cell numbers/microliter whole blood for a CD56^dim; b CD62L⁻CD57⁻; c CD62L⁻CD57⁺; d CD62L⁺CD57⁻; e CD62L⁺CD57⁺; f CD27⁺CD69⁻CD62L⁻CD57⁻; g CD27⁺CD69⁻CD62L⁻CD57⁺; h CD27⁺CD69⁻CD62L⁺CD57⁻; i CD27⁺CD69⁻CD62L⁺CD57⁺. The box indicates the 25th, 50th, and 75th percentiles; the whiskers the minimum and maximum values excluding outliers. Wilcoxon rank-sum test was used to test for differences and p values <0.05 are reported

Fig. 3

CD56^bright NK cells. Cells were gated as described in Supplementary Fig. 2. Shown are boxplots for frequencies and total cell numbers/microliter whole blood for a total CD56; b CD56^bright; c CD62L⁺CD57⁻; d CD27⁺CD69⁻CD62L⁺CD57⁻. The box indicates the 25th, 50th, and 75th percentiles; the whiskers the minimum and maximum values excluding outliers. Wilcoxon rank-sum test was used to test for differences and p values <0.05 are reported