Peripheral blood dendritic cells and monocytes are differently regulated in the elderly
Introduction
Aged people suffer increased incidence of morbidity and mortality from infections, have a reduced capacity to generate robust protective immune responses upon vaccination, and are more likely to develop selected cancer and autoimmune disorders. These clinical problems may be ascribed at least in part to the ageing of the immune system, referred to as immunosenescence, that is associated with a state of dysregulation and overall deterioration of immune function [1]. The adaptive immune system is heavily affected in immunosenescence, with a well-documented decline in humoral as well as cell-mediated immune responses. Although marginal alterations in B lymphocytes are apparent, the decline in immune responses is mainly consequent to alterations of T cells that are more susceptible to immunosenescence [2], [3], [4], [5], [6], [7]. The impact of ageing on the innate immune system is less defined. Innate immunity has long been considered a separate entity from adaptive immunity, but interest in it is now growing based on the knowledge of its integration with specific immune effectors and its key role in stimulating the response of adaptive immunity. Recent reviews have addressed the impact of ageing on macrophages and NK cells [8], [9], while the effects of ageing on dendritic cells (DCs) have been poorly investigated so far.
DCs are the single most central player in all immune responses. They are professional antigen-presenting cells unique in their ability to prime naive T cells in vivo, and exceptionally potent immunogens under inflammatory conditions [10], [11]. Yet, DCs are also critical to the induction and maintenance of self-tolerance, through multiple mechanisms that include T cell deletion and anergy as well as the generation of regulatory T cells [12], [13], [14]. The possibility that age-related alterations of DCs may contribute to the dysregulation of the adaptive immunity observed in the elderly may therefore deserve consideration.
Aim of the present study was therefore to investigate DCs in the elderly. For this purpose, we enumerated and characterized DCs in the peripheral blood, that is the most accessible source of DCs. Peripheral blood DCs (PBDCs) from healthy subjects aged 20–92 years were analyzed using flow cytometric methods that allow cell enumeration and characterization directly in whole peripheral blood samples [15], [16]. The analysis was extended to circulating CD34+ cells and monocytes, that both represent DC precursors.
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Subjects
Seventy subjects (32 males, 38 females) aged 20–92 years with a uniform distribution among 10-year age intervals were included in the study. Older volunteers (> 70 years) were recruited from our Geriatrics outpatient's department. They had, during the last 3 years, a full medical examination every 12 months by the physicians from the Geriatrics Unit. To target the study on a population representative of the majority of elderly people, we did not stringently apply all the criteria of the
Enumeration of PBDCs, CD34+ precursors and monocytes in the peripheral blood
The percentage of PBDCs in the mononuclear cell population and their absolute number in peripheral blood samples progressively declined with increasing age. A significant inverse correlation was observed between age expressed in years and both the percentage of PBDCs (r = − 0.467, p < 0.001) and their number (r = − 0.331, p = 0.007) (Fig. 1A). To define a possible cut-off age able to reveal DC differences between young and old individuals, we analyzed the number of PBDCs in individuals arbitrarily
Discussion
In this study we investigated the effects of ageing on the number, phenotype and function of PBDCs, to assess whether DC alterations may contribute to the state of immune dysregulation that affects aged people. We chose to study PBDCs because peripheral blood is the most accessible source of DCs. We applied flow cytometric methods that allow the enumeration and characterization of DCs directly in whole peripheral blood samples, without any ex vivo enrichment. With these methods, that directly
Acknowledgments
This work was supported in part by grants from Ministero dell'Istruzione, dell'Università e della Ricerca, cofinanziamento 2003 (2003069391-001) (MLV).
We thank Elisa Vaccaroni for expert technical assistance.
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