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Immunology and Transplantation

Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice Is Controlled by Allelic Variants of Idd3

  1. Todd Pearson1,
  2. Peter Weiser2,
  3. Thomas G. Markees2,
  4. David V. Serreze123,
  5. Linda S. Wicker4,
  6. Laurence B. Peterson5,
  7. Anne-Marie Cumisky5,
  8. Leonard D. Shultz123,
  9. John P. Mordes2,
  10. Aldo A. Rossini126 and
  11. Dale L. Greiner12
  1. 1Program in Immunology and Virology, The University of Massachusetts Medical School, Worcester, Massachusetts
  2. 2Department of Medicine, The University of Massachusetts Medical School, Worcester, Massachusetts
  3. 3The Jackson Laboratory, Bar Harbor, Maine
  4. 4Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, University of Cambridge, Cambridge, U.K
  5. 5Department of Pharmacology, Merck Research Laboratories, Rahway, New Jersey
  6. 6Program in Molecular Medicine, The University of Massachusetts Medical School, Worcester, Massachusetts
  1. Address correspondence and reprint requests to Dale L. Greiner, PhD, University of Massachusetts Medical School, 373 Plantation St., Biotech 2, Suite 218, Worcester, MA 01605. E-mail: dale.greiner{at}umassmed.edu
Diabetes 2004 Aug; 53(8): 1972-1978. https://doi.org/10.2337/diabetes.53.8.1972
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    FIG. 1.

    Life table analysis of islet allograft survival in chemically diabetic mice. Groups of 6- to 8-week old chemically diabetic mice were given C3H/HeJ islet allografts as described in research design and methods. A: Mice were also treated with a DST plus anti-CD154 mAb. DST (107 C3H/HeJ spleen cells) was given on day −7 relative to transplantation, and anti-CD154 mAb (0.5 mg/dose) was given on days −7, −4, 0, and 4. B: Mice were treated with anti-CD154 mAb monotherapy (0.5 mg/dose), which was given on days −7, −4, 0, and 4 relative to transplantation. C: Mice received allografts but no other treatment. The experiment was terminated arbitrarily at various time points as mice were used for other experiments. Vertical bars incidate mice that were removed from the study with intact grafts or alive with intact grafts at the conclusion of the period of observation.

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    FIG. 2.

    Improved NKT cell function in (NOD × C57BL/6)F1 mice. Expression of IL-4 mRNA was measured by real-time quantitative PCR from whole spleen 90 min after anti-CD3 (1 μg/mouse) stimulation in vivo. Relative levels of mRNA (ΔCT) from individual mice are expressed as the IL-4 cycle threshold (CT) detection value minus the glyceraldehyde-3-phosphate dehydrogenase cycle threshold value. Every unit increase in ΔCT represents a twofold decrease in mRNA expression. In the data shown, NOD has eightfold less IL-4 mRNA than C57BL/6 and fourfold less IL-4 mRNA than (C57BL/6 × NOD)F1.

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August 2004, 53(8)
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Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice Is Controlled by Allelic Variants of Idd3
Todd Pearson, Peter Weiser, Thomas G. Markees, David V. Serreze, Linda S. Wicker, Laurence B. Peterson, Anne-Marie Cumisky, Leonard D. Shultz, John P. Mordes, Aldo A. Rossini, Dale L. Greiner
Diabetes Aug 2004, 53 (8) 1972-1978; DOI: 10.2337/diabetes.53.8.1972

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Islet Allograft Survival Induced by Costimulation Blockade in NOD Mice Is Controlled by Allelic Variants of Idd3
Todd Pearson, Peter Weiser, Thomas G. Markees, David V. Serreze, Linda S. Wicker, Laurence B. Peterson, Anne-Marie Cumisky, Leonard D. Shultz, John P. Mordes, Aldo A. Rossini, Dale L. Greiner
Diabetes Aug 2004, 53 (8) 1972-1978; DOI: 10.2337/diabetes.53.8.1972
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