Effect of Aging on Bone Marrow-Derived Murine CD11c+CD4-CD8 - Dendritic Cell Function

Grolleau-Julius, Annabelle; Garg, Monika R.; Mo, Ru Ran; Stoolman, Lloyd L.; Yung, Raymond

doi:10.1093/gerona/61.10.1039

Cited by 64 publications

(66 citation statements)

References 52 publications

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“…Nevertheless, the affinity of MD to the C-type lectin DC-SIGN has been previously demonstrated [27]. DC-SIGN abundantly expressed in both human and mouse DC recognizes complex mannose residues and targets the late endolysosome [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

et al. 2008

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Antigen mannosylation has been shown to be an effective approach to potentiate antigen immunogenicity, due to the enhanced antigen uptake and presentation by APC. To overcome disadvantages associated with conventional methods used to mannosylate antigens, we have developed a novel mannose-based antigen delivery system that utilizes a polyamidoamine (PAMAM) dendrimer. It is demonstrated that mannosylated dendrimer ovalbumin (MDO) is a potent immune inducer. With a strong binding avidity to DC, MDO potently induced OVA-specific T cell response in vitro. It was found that the immunogenicity of MDO was due not only to enhanced antigen presentation, but also to induction of DC maturation. Mice immunized with MDO generated strong OVA-specific CD4 + /CD8 + T cell and antibody responses. MDO also targeted lymph node DC to crosspresent OVA, leading to OTI CD8 + T cell proliferation. Moreover, upon challenge with B16-OVA tumor cells, tumors in mice pre-immunized with MDO either did not grow or displayed a much more delayed onset, and had slower kinetics of growth than those of OVA-immunized mice. This mannose-based antigen delivery system was applied here for the first time to the immunization study. With several advantages and exceptional adjuvanticity, we propose mannosylated dendrimer as a potential vaccine carrier.

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Section: Discussionmentioning

confidence: 99%

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

et al. 2008

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“…On the other hand, DC differentiated in vitro from precursors obtained from the bone marrow of old mice show an increased secretion of IL-10 and a reduced secretion of tumor necrosis factor alpha (TNF-α) and IL-6 after stimulation with lipopolysaccharide compared to the DC obtained from young mice (14).…”

Section: Introductionmentioning

confidence: 99%

Effect of aging and oral tolerance on dendritic cell function

Simioni¹,

Fernandes²,

Gabriel³

et al. 2010

Braz J Med Biol Res

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“…Importantly, aged C57BL/6 mice lost their resistance to mousepox due to a decrease in numbers of NKs and impaired trafficking, a phenomenon not found in several other mouse strains (15). For DCs, aging leads to decreased dendritic cell-specific CD209 (DC-SIGN) expression on immature bone marrow-derived cells (BMDCs) without affecting their function in T-cell priming and Toll-like receptor (TLR) response (16,17). In a tumor antigen system, BMDCs from aged mice were less efficient in stimulating antigen-specific T cells and displayed defective trafficking (18).…”

mentioning

confidence: 99%

Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication

Guo

Tilburgs

Wong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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The reciprocal activation of dendritic cells (DCs) and natural killer cells (NKs) plays a key role in both innate and adaptive immunity. The effect of aging on this cross-talk, a critical step in virus disease control and tumor immunology, has not been reported. Splenic DCs and NKs were purified from both young and old C57BL/6 mice and cocultured in the presence of polyinosinic:polycytidylic acid (poly I:C). The resulting activation of NKs was measured as expression of CD69 and secretion of IFN-γ. However, DCs from old mice could not activate NKs from either young or old mice in vitro or in vivo. In contrast, DCs from young mice efficiently activated NKs from both young and old mice. DCs from old mice were deficient in poly I: C-stimulated secretion of IL-15, IL-18, and IFN-α. Gene expression analysis revealed many other differences between DCs of old and young mice. Young mice strongly eradicated MHC class I-negative NK-sensitive RMA-S lymphoma mutant tumor cells, but old mice did not, in concert with the previous report that mousepox kills aged, but not young, C57BL/6 mice. Furthermore, a similar dysfunction of DC and its key role in NK activation was found in 27 out of 55 healthy human donors. A few years later, the reciprocal interaction of DCs and NKs during viral infection was also described (3). Cytokines from DCs as well as cell-cell contact were shown to enhance NK function. DCs secreted IL-12 and IL-18, which promoted cytokine production by NKs (4, 5). Further, membrane-bound IL-15/15Rα on DCs is important in promoting NK survival and proliferation (6-8), and type I IFNs are crucial in the induction of NK cytotoxicity. In addition, some surface molecules on DCs-for example, CD40, CD48, CD70, CD80, CD86, major histocompatibility complex class I-related chain A/B (MICA/B), leukocyte function-associated Ag-1 (LFA-1), and chemokine (C-X3-C motif) ligand 1 (CX3CL1)-have been reported to be involved in the effect of DCs on NKs (1).It is well known that aged humans are more susceptible to malignancies and infectious diseases and less responsive to vaccination because of immunosenescence-that is, progressive deterioration in immune function with aging. Increasing evidence shows aging affects many cells in both innate immunity and adaptive immunity (9). For example, impairment of DC and macrophage functions, including phagocytic activity, cytokine secretion, wound repair, and antigen presentation, were observed (10, 11). In T cells, a shift from the naïve to memory phenotype, a decreased proliferative response, and impaired cytolytic activity were found (12). Some of these defects in cell functions are intrinsic, whereas others might be the consequence of the complicated interactions between immune cells (13). As key cells in innate immunity, functional changes in both NKs and DCs with aging were described. For example, increased numbers of NKs, decreased NK cytotoxicity on a per-cell basis, and reduced levels of cytokines and chemokines upon activation were reported in humans (14). Importantly, aged C57BL/6 mi...

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Effect of Aging on Bone Marrow-Derived Murine CD11c+CD4-CD8 - Dendritic Cell Function

Cited by 64 publications

References 52 publications

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

Effect of aging and oral tolerance on dendritic cell function

Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication

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