Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

• John A. Todd ,

  * E-mail: fw211@cam.ac.uk (FWL); john.todd@well.ox.ac.uk (JAT)

  Current address: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

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• Marina Evangelou ,

  Contributed equally to this work with: Marina Evangelou, Antony J. Cutler, Marcin L. Pekalski, Neil M. Walker, Helen E. Stevens

  Affiliation Department of Mathematics, Imperial College London, London, United Kingdom

  http://orcid.org/0000-0003-0789-8944

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• Antony J. Cutler ,

  Contributed equally to this work with: Marina Evangelou, Antony J. Cutler, Marcin L. Pekalski, Neil M. Walker, Helen E. Stevens

  Current address: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

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• Marcin L. Pekalski ,

  Contributed equally to this work with: Marina Evangelou, Antony J. Cutler, Marcin L. Pekalski, Neil M. Walker, Helen E. Stevens

  Current address: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

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• Neil M. Walker ,

  Contributed equally to this work with: Marina Evangelou, Antony J. Cutler, Marcin L. Pekalski, Neil M. Walker, Helen E. Stevens

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Helen E. Stevens ,

  Contributed equally to this work with: Marina Evangelou, Antony J. Cutler, Marcin L. Pekalski, Neil M. Walker, Helen E. Stevens

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Linsey Porter,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

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• Deborah J. Smyth,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Daniel B. Rainbow,

  Current address: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Ricardo C. Ferreira,

  Current address: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Laura Esposito,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0003-3246-7855

  ⨯
• Kara M. D. Hunter,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0002-8089-0693

  ⨯
• Kevin Loudon,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0001-9055-6894

  ⨯
• Kathryn Irons,

  Affiliation National Institute for Health Research Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom

  http://orcid.org/0000-0002-7843-7080

  ⨯
• Jennie H. Yang,

  Affiliation Department of Immunobiology, Faculty of Life Sciences & Medicine, King’s College London, National Institute of Health Research Biomedical Research Centre, Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London, London, United Kingdom

  ⨯
• Charles J. M. Bell,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Helen Schuilenburg,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• James Heywood,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0002-2499-3663

  ⨯
• Ben Challis,

  Affiliation Wellcome Trust/MRC Institute of Metabolic Science, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom

  ⨯
• Sankalpa Neupane,

  Affiliation Wellcome Trust/MRC Institute of Metabolic Science, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom

  http://orcid.org/0000-0001-9519-0940

  ⨯
• Pamela Clarke,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Gillian Coleman,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Sarah Dawson,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Donna Goymer,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Katerina Anselmiova,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0002-9533-100X

  ⨯
• Jane Kennet,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Judy Brown,

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Sarah L. Caddy,

  Affiliation Division of Virology, Department of Pathology, Addenbrooke’s Hospital, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Jia Lu,

  Affiliation Division of Virology, Department of Pathology, Addenbrooke’s Hospital, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0003-3995-324X

  ⨯
• Jane Greatorex,

  Affiliation Public Health England, Clinical Microbiology and Public Health Laboratory, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom

  ⨯
• Ian Goodfellow,

  Affiliation Division of Virology, Department of Pathology, Addenbrooke’s Hospital, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
• Chris Wallace,

  Affiliations JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom, MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, United Kingdom

  http://orcid.org/0000-0001-9755-1703

  ⨯
• Tim I. Tree,

  Affiliation Department of Immunobiology, Faculty of Life Sciences & Medicine, King’s College London, National Institute of Health Research Biomedical Research Centre, Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London, London, United Kingdom

  http://orcid.org/0000-0002-6973-5377

  ⨯
• Mark Evans,

  Affiliation Wellcome Trust/MRC Institute of Metabolic Science, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, Cambridge, United Kingdom

  ⨯
• Adrian P. Mander,

  Affiliation MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, United Kingdom

  ⨯
• Simon Bond,

  Affiliations National Institute for Health Research Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge, United Kingdom, MRC Biostatistics Unit Hub for Trials Methodology Research, Cambridge Institute of Public Health, Cambridge Biomedical Campus, Cambridge, United Kingdom

  ⨯
• Linda S. Wicker,

  Current address: Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  ⨯
•  [ ... ],
• Frank Waldron-Lynch

  * E-mail: fw211@cam.ac.uk (FWL); john.todd@well.ox.ac.uk (JAT)

  Current address: Experimental Medicine and Immunotherapeutics, Department of Medicine, School of Clinical Medicine, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  Affiliation JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Biomedical Campus, University of Cambridge, Cambridge, United Kingdom

  http://orcid.org/0000-0002-0597-4328

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