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West Ashley Library
9 a.m. - 7 p.m.
Phone: (843) 766-6635
Folly Beach Library
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Phone: (843) 588-2001
Edgar Allan Poe/Sullivan's Island Library
Closed for renovations
Phone: (843) 883-3914
Wando Mount Pleasant Library
9 a.m. - 8 p.m.
Phone: (843) 805-6888
Village Library
9 a.m. - 1 p.m.
Phone: (843) 884-9741
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Otranto Road Library
9 a.m. - 8 p.m.
Phone: (843) 572-4094
Mt. Pleasant Library
9 a.m. - 8 p.m.
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McClellanville Library
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Keith Summey North Charleston Library
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9 a.m. - 8 p.m.
Phone: (843) 559-1945
Hurd/St. Andrews Library
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Miss Jane's Building (Edisto Library Temporary Location)
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Dorchester Road Library
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Phone: (843) 722-7550
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Phone: (843) 805-6930
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Reversal of Diabetes in NOD Mice by Clinical-Grade Proinsulin and IL-10-Secreting Lactococcus lactis in Combination With Low-Dose Anti-CD3 Depends on the Induction of Foxp3-Positive T Cells.
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- Author(s): Takiishi, Tatiana; Cook, Dana Paulina; Korf, Hannelie; Sebastiani, Guido; Mancarella, Francesca; Carvalho Mori Cunha, João Paulo Monteiro; Wasserfall, Clive; Casares, Noelia; Lasarte, Juan José; Steidler, Lothar; Rottiers, Pieter; Dotta, Francesco; Gysemans, Conny; Mathieu, Chantal; Cunha, João Paulo Monteiro Carvalho Mori
- Source:
Diabetes; Feb2017, Vol. 66 Issue 2, p448-459, 12p, 7 Graphs- Subject Terms:
TREATMENT of diabetes; LABORATORY mice; PROINSULIN; LACTOCOCCUS lactis; CD3 antigen; T cells; AUTOANTIGENS; INTERLEUKIN-10; ANIMALS; ANTIGENS; BIOLOGICAL models; BLOOD sugar; DIABETES; GLUCOSE tolerance tests; GROWTH factors; IMMUNOGLOBULINS; IMMUNOLOGICAL tolerance; IMMUNOLOGY technique; INTERLEUKINS; LACTOBACILLUS; MICE; PANCREAS; PROTEINS - Source:
- Additional Information
- Abstract: The introduction of β-cell autoantigens via the gut through Lactococcus lactis (L. lactis) has been demonstrated to be a promising approach for diabetes reversal in NOD mice. Here we show that a combination therapy of low-dose anti-CD3 with a clinical-grade self-containing L. lactis, appropriate for human application, secreting human proinsulin and interleukin-10, cured 66% of mice with new-onset diabetes, which is comparable to therapy results with plasmid-driven L. lactis Initial blood glucose concentrations (<350 mg/dL) and insulin autoantibody positivity were predictors of the stable reversal of hyperglycemia, and decline in insulin autoantibody positivity was an immune biomarker of therapeutic outcome. The assessment of the immune changes induced by the L. lactis-based therapy revealed elevated frequencies of CD4+Foxp3+ T cells in the pancreas-draining lymph nodes, pancreas, and peripheral blood of all treated mice, independent of metabolic outcome. Neutralization of cytotoxic T-lymphocyte antigen 4 and transforming growth factor-β partially abrogated the suppressive function of therapy-induced regulatory T cells (Tregs). Ablation or functional impairment of Foxp3+ Tregs in vivo at the start or stop of therapy impaired immune tolerance, highlighting the dependence of the therapy-induced tolerance in mice with new-onset diabetes on the presence and functionality of CD4+Foxp3+ T cells. Biomarkers identified in this study can potentially be used in the future to tailor the L. lactis-based combination therapy for individual patients. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Diabetes is the property of American Diabetes Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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