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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      The migration of synthetic magnetic nanoparticle labeled dendritic cells into lymph nodes with optical imaging

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          Abstract

          Background

          The successful biotherapy of carcinoma with dendritic cell (DC) vaccines pivotally relies on DCs’ migratory capability into lymph tissues and activation of T cells. Accurate imaging and evaluation of DC migration in vivo have great significance during antitumor treatment with DC vaccine. We herein examined the behavior of DCs influenced by synthetic superparamagnetic iron oxide (SPIO) nanoparticle labeling.

          Methods

          γ-Fe 2O 3 nanoparticles were prepared and DCs, which were induced from bone marrow monocytes of enhanced green fluorescent protein (EGFP) transgenic mice, were labeled. The endocytosis of the SPIO, surface molecules, cell apoptosis and fluorescence intensity of EGFP-DCs were displayed by Prussian blue staining and flow cytometry (FCM), respectively. After EGFP-DCs, labeled with SPIO, were injected into footpads (n = 5) for 24 hours, the mice were examined in vivo by optical imaging (OPI). Meanwhile, confocal imaging and FCM were applied, respectively, to detect the migration of labeled DCs into draining lymph nodes.

          Results

          Nearly 100% of cells were labeled by the SPIO, in which the intracellular blue color gradually deepened and the iron contents rose with the increase of labeling iron concentrations. In addition, cell apoptosis and the surface molecules on DCs were at similar levels after SPIO labeling. After confirming that the fluorescence intensity of EGFP on DCs was not influenced by SPIO, the homing ability of EGFP-DCs labeled with SPIO displayed that the fluorescence intensity and the ratios of EGFP-DCs in draining lymph nodes were gradually decreased with the increase of labeling iron concentrations.

          Conclusion

          The synthetic SPIO nanoparticles possess perfect labeling ability and biocompatibility. Moreover, DCs labeled with a low dose of SPIO showed stronger migratory capability in vivo.

          Most cited references23

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          Regulation of Dendritic Cell Migration to the Draining Lymph Node

          Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7+/+ DCs migrating to the draining lymph node, but not CCR7−/− DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4+ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor necrosis factor that conditioned the tissue for increased DC migration. These results indicate that DC number and tissue inflammation are critical parameters for DC-based vaccination.
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            Effective migration of antigen-pulsed dendritic cells to lymph nodes in melanoma patients is determined by their maturation state.

            Dendritic cells are the professional antigen-presenting cells of the immune system. To induce an effective immune response, these cells should not only express high levels of MHC and costimulatory molecules but also migrate into the lymph nodes to interact with naïve T cells. Here, we demonstrate that in vitro-generated mature, but not immature dendritic cells, efficiently migrate into the T-cell areas of lymph nodes of melanoma patients. This difference is confirmed by in vitro studies, in which immature dendritic cells are strongly adherent, whereas mature dendritic cells remain highly motile. Our present findings demonstrate that the ability of dendritic cells to mount a proper immune response correlates with their ability to migrate both in vitro and in vivo.
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              Tumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolism.

              Dendritic cells (DC) have a critical effect on the outcome of adaptive immune responses against growing tumors. Whereas it is generally assumed that the presence of phenotypically mature DCs should promote protective antitumor immunity, evidence to the contrary does exist. We describe here a novel mechanism by which tumor-infiltrating dendritic cells (TIDC) actively contribute to the suppression of protective CD8(+) T-cell-based antitumor immunity. Using the BALB/NeuT model of spontaneously arising mammary carcinoma, we found that canonical MHC II(+)/CD11b(+)/CD11c(high) TIDCs act as regulatory DCs to suppress CD8(+) T-cell function, resulting in diminished T-cell-based antitumor immunity in vivo. Stimulation of naive T cells with regulatory TIDCs resulted in an altered cell fate program characterized by minimal T-cell expansion, impaired IFNgamma production, and anergy. Suppression by regulatory TIDCs overcame stimulatory signals provided by standard DCs, occurred in the absence of cognate interactions with T cells, and was mediated primarily by arginase metabolism of l-arginine. Immunosuppressive TIDCs were found in every murine tumor type examined and were phenotypically distinct from tumor-infiltrating CD11c(int-low)/CD11b(+)/Gr-1(+) myeloid-derived suppressor cells. Thus, within the tumor microenvironment, MHC II(+) TIDCs can function as potent suppressors of CD8(+) T-cell immunity.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2013
                2013
                07 October 2013
                : 8
                : 3737-3744
                Affiliations
                [1 ]Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, Nanjing, People’s Republic of China
                [2 ]Jiangsu Key Lab of Molecular and Function Imaging, Department of Radiology
                [3 ]Department of Hematology, Zhongda Hospital, Medical School
                [4 ]State Key Laboratory of Molecule and Bimolecular Electronics, Jiangsu Provincial Laboratory for Biomaterials and Devices; Southeast University, Nanjing, People’s Republic of China
                [5 ]Leeds Dental Institute, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom
                Author notes
                Correspondence: Qingang Hu, Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, 30 Zhongyang Road, Nanjing 210008, People’s Republic of China, Tel +86 25 8362 0101, Fax +86 25 8362 0101, Email qghu@ 123456nju.edu.cn
                Yongbin Mou, Center Laboratory of Stomatology, Stomatological Hospital Affiliated Medical School, Nanjing University, 30 Zhongyang Road, Nanjing 210008, People’s Republic of China, Tel +86 25 8362 0236, Fax +86 25 8362 0101, Email yongbinmou@ 123456gmail.com
                [*]

                These authors contributed equally to this work

                Article
                ijn-8-3737
                10.2147/IJN.S52135
                3795011
                24124362
                27296216-3322-4e83-9e7f-d98a49ac7cf2
                © 2013 Su et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Molecular medicine
                optical imaging,dendritic cell,superparamagnetic iron oxide,cell tracking
                Molecular medicine
                optical imaging, dendritic cell, superparamagnetic iron oxide, cell tracking

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