Peripheral blood dendritic cells and monocytes are differently regulated in the elderly

Bella, Silvia Della; Bierti, L.; Presicce, Pietro; Arienti, Rossana; Valenti, Marta; Saresella, Marina; Vergani, Carlo; Villa, Maria Luisa

doi:10.1016/j.clim.2006.09.012

Cited by 241 publications

(125 citation statements)

References 39 publications

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“…Taken together, these observations suggest that the alterations observed in DC with age can be linked to an impaired potential of aged bone marrow to generate DC. Although the mechanisms affected by age in dendropoiesis are still not completely clear, candidates such as a decreased frequency of CD34+ cells (Della Bella et al 2007) as well as an altered response to DC differentiation factors such as FLT3-ligand (Shurin et al 1997(Shurin et al , 2004 have been described.…”

Section: Discussionmentioning

confidence: 98%

Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design

et al. 2008

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It is known that immune system functions decrease with age, and that adaptive immune responses, especially CD4+ T cell function, seem to be the main affected point in immunity with aging. Dendritic cells (DC) are the major antigen presenting cell (APC), and at least part of the defects observed in adaptive immunity of aged individuals could be due to diminished potential of bone marrow to generate new DC, or defects in DC function. In this study, we investigated if the ability of aged bone marrow (BM) to generate new DC in vitro, as well as aged BM-derived DC responses to lypopolysaccharide (LPS). Because DC are important tools in newly developing anti-tumor therapies, we also studied the ability of aged DC to phagocytose and present antigen from necrotic tumor cells. We found that aged BM generated fewer DC in vitro compared to young BM. While LPS-induced DC maturation is reduced in DC of aged mice, a high TNF-alpha production is observed in aged DC even without LPS stimulation. While phagocytosis of tumor cells is not affected by age, and DC derived from aged BM show a higher TNF-alpha production in response to phagocytosis, presentation of tumor antigens was decreased in aged DC. Because class II upregulation in response to phagocytosis was similar between aged and young DC, this could indicate an age associated processing defect in the exogenous pathway. These findings suggest that age of BM used to generate DC does not impair their phagocytic ability or TNF-alpha production, however leads to a decreased yield in mature DC, reduced response to LPS, and diminished antigen processing/presentation potential. Our results are relevant to optimization DC-based vaccine design for aged populations.

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Section: Discussionmentioning

confidence: 98%

Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design

et al. 2008

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“…Conflicting findings have been reported with regard to the age-related changes in pDC from elderly persons. At least two studies demonstrated an age-related decline[25,26], whereas two other studies showed no changes in the numbers of pDC with aging[22,23]. Some have suggested that the decline in pDC numbers results from the selective cell death of pDC during the process of isolating PBMC from whole blood[22].…”

Section: Discussionmentioning

confidence: 99%

“…At least two studies demonstrated an age-related decline[25,26], whereas two other studies showed no changes in the numbers of pDC with aging[22,23]. Some have suggested that the decline in pDC numbers results from the selective cell death of pDC during the process of isolating PBMC from whole blood[22]. However, a more recent study argued against this notion and proposed that insufficient numbers of cells acquired during the flow cytometry analysis produced inconsistent findings with age.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies examining the role of DC in human aging have resulted in conflicting results[21]. In one study for mDC, it was reported that elderly subjects had lower numbers of mDC in their peripheral blood compared with young subjects, and mDC from elderly subjects secreted less IL-12 than young subjects after stimulation by lipopolysaccaride (LPS)[22]. In contrast, this age-related decline in mDC in peripheral blood was not observed in the report by Agrawal et al [23].…”

Section: Introductionmentioning

confidence: 99%

“…With regard to pDC, it was reported that aging was associated with a decline in frequency and absolute cell counts in pDC found in peripheral blood[25,26]. However, a recent paper by Della Bella et al showed that the number of pDC in peripheral blood was not affected by aging[22]. To date, there is no consensus as to how DC subsets are affected by the aging process.…”

Section: Introductionmentioning

confidence: 99%

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Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood

et al. 2009

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Dendritic cells (DC) are potent antigen-presenting cells that initiate and regulate T-cell responses. In this study, the numbers and functional cytokine secretions of plasmacytoid and myeloid DC (pDC and mDC, respectively) in peripheral blood from young and elderly subjects were compared. Overall, pDC numbers in peripheral blood were lower in healthy elderly compared with healthy young subjects (p = 0.016). In response to influenza virus stimulation, isolated pDC from healthy elderly subjects secreted less interferon (IFN)–α compared with those from healthy young subjects. The decline in IFN-α secretion was associated with a reduced proportion of pDC that expressed Toll-like receptor–7 or Toll-like receptor-9. In contrast, there was little difference in the numbers and cytokine secretion function between healthy young and healthy elderly subjects (p = 0.82). However, in peripheral blood from frail elderly subjects, the numbers of mDC were severely depleted as compared with either healthy young or elderly subjects (p = 0.014 and 0.007, respectively). Thus, aging was associated with the numerical and functional decline in pDC, but not mDC, in healthy young versus elderly subject group comparisons, while declining health in the elderly can profoundly impact mDC negatively. Because of the importance of pDC for antiviral responses, the age-related changes in pDC likely contribute to the impaired immune response to viral infections in elderly persons, especially when combined with the mDC dysfunction occurring in those with compromised health.

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A six‐color flow cytometric assay for the analysis of peripheral blood dendritic cells

Giannelli¹,

Taddeo²,

Presicce³

et al. 2008

Cytometry Part B Clinical

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Background: Flow cytometric analysis of peripheral blood dendritic cells (PBDCs) and their myeloid (mDCs) and plasmacytoid (pDCs) subsets is a less invasive procedure that is acquiring growing clinical relevance. Because dendritic cells (DCs) lack unique lineage markers, current methods that are based on 3-or 4-color assays do not allow multiparametric analysis of DC subsets. In this study a dedicated 6-color assay was developed.Methods: mDCs and pDCs were counted and characterized for the expression of activation/maturation markers by using a single-platform 6-color assay. Whole-blood samples from 20 healthy controls were directly stained with either CD80-FITC/CD40-PE/lineage-PerCP-Cy5.5/CD123-PE-Cy7/CD11c-APC/HLA-DR-APC-Cy7 or CD86-FITC/CD83-PE/lineage-PerCP-Cy5.5/CD123-PE-Cy7/CD11c-APC/HLA-DR-APC-Cy7 combination, in the presence of commercial fluorospheres. A dual-platform 3-color assay currently in use was run in parallel for comparison.Results: The 6-color assay provided mDCs and pDCs counts similar to counts obtained by the 3-color assay. Only the 6-color assay could show differential expression of activation markers by mDCs and pDCs, with pDCs expressing lower levels of costimulatory molecules and HLA-DR, but higher levels of CD83.Conclusions: The 6-color assay described here may be a sensitive tool for assessing possible variations in the number and features of mDCs and pDCs whose reciprocal balance is critical in understanding the more detailed orchestration of immune responses. q

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Peripheral blood dendritic cells and monocytes are differently regulated in the elderly

Cited by 241 publications

References 39 publications

Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design

Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design

Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood

A six‐color flow cytometric assay for the analysis of peripheral blood dendritic cells

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