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Loss of immune tolerance to IL-2 in type 1 diabetes

Author

Listed:
  • Louis Pérol

    (Sorbonne Universités, Pierre and Marie Curie University Paris 06
    Centre National de la Recherche Scientifique, UMR 7211
    Institut National de la Santé et de la Recherche Médicale (INSERM), U 959, Immunology- Immunopathology-Immunotherapy (I3)
    Institut Curie, PSL Research University, INSERM U932)

  • John M. Lindner

    (Novartis Institutes for Biomedical Research)

  • Pamela Caudana

    (Institut Curie, PSL Research University, INSERM U932
    SiRIC TransImm Translational Immunotherapy Team, Research Center, PSL Research University, Institut Curie
    Centre d’Investigation Clinique Biothérapie CICBT 1428, Institut Curie)

  • Nicolas Gonzalo Nunez

    (Institut Curie, PSL Research University, INSERM U932
    SiRIC TransImm Translational Immunotherapy Team, Research Center, PSL Research University, Institut Curie
    Centre d’Investigation Clinique Biothérapie CICBT 1428, Institut Curie)

  • Audrey Baeyens

    (Sorbonne Universités, Pierre and Marie Curie University Paris 06
    Centre National de la Recherche Scientifique, UMR 7211
    Institut National de la Santé et de la Recherche Médicale (INSERM), U 959, Immunology- Immunopathology-Immunotherapy (I3))

  • Andrea Valle

    (Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute)

  • Christine Sedlik

    (Institut Curie, PSL Research University, INSERM U932
    SiRIC TransImm Translational Immunotherapy Team, Research Center, PSL Research University, Institut Curie
    Centre d’Investigation Clinique Biothérapie CICBT 1428, Institut Curie)

  • Delphine Loirat

    (SiRIC TransImm Translational Immunotherapy Team, Research Center, PSL Research University, Institut Curie
    Centre d’Investigation Clinique Biothérapie CICBT 1428, Institut Curie)

  • Olivier Boyer

    (INSERM, U905
    Normandie Univ. IRIB
    Rouen University Hospital, Laboratory of Immunology)

  • Alain Créange

    (Service de Neurologie, Groupe Hospitalier Henri Mondor, AP-HP
    EA 4391, Université Paris Est)

  • José Laurent Cohen

    (Université Paris-Est Créteil
    INSERM U 955, Institut Mondor de Recherche Biomédicale (IMRB)
    AP-HP, Groupe Hospitalier Henri-Mondor Albert-Chenevier)

  • Ute Christine Rogner

    (Institut Pasteur, CNRS URA 2578)

  • Jun Yamanouchi

    (Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine. University of Calgary)

  • Martine Marchant

    (Novartis Institutes for Biomedical Research)

  • Xavier Charles Leber

    (Novartis Institutes for Biomedical Research)

  • Meike Scharenberg

    (Novartis Institutes for Biomedical Research)

  • Marie-Claude Gagnerault

    (INSERM, U1016, Cochin Institute, DeAR Lab
    Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Diabétologie
    Paris Descartes University, Sorbonne Paris Cité, Faculté de Médecine)

  • Roberto Mallone

    (INSERM, U1016, Cochin Institute, DeAR Lab
    Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Diabétologie
    Paris Descartes University, Sorbonne Paris Cité, Faculté de Médecine)

  • Manuela Battaglia

    (Diabetes Research Institute (DRI), IRCCS San Raffaele Scientific Institute)

  • Pere Santamaria

    (Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine. University of Calgary
    Institut D’Investigacions Biomediques August Pi i Sunyer)

  • Agnès Hartemann

    (Université Pierre et Marie Curie—Paris 6
    Nutrition and Diabetes, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière-Charles Foix Hospital)

  • Elisabetta Traggiai

    (Novartis Institutes for Biomedical Research)

  • Eliane Piaggio

    (Sorbonne Universités, Pierre and Marie Curie University Paris 06
    Centre National de la Recherche Scientifique, UMR 7211
    Institut National de la Santé et de la Recherche Médicale (INSERM), U 959, Immunology- Immunopathology-Immunotherapy (I3)
    Institut Curie, PSL Research University, INSERM U932)

Abstract

Type 1 diabetes (T1D) is characterized by a chronic, progressive autoimmune attack against pancreas-specific antigens, effecting the destruction of insulin-producing β-cells. Here we show interleukin-2 (IL-2) is a non-pancreatic autoimmune target in T1D. Anti-IL-2 autoantibodies, as well as T cells specific for a single orthologous epitope of IL-2, are present in the peripheral blood of non-obese diabetic (NOD) mice and patients with T1D. In NOD mice, the generation of anti-IL-2 autoantibodies is genetically determined and their titre increases with age and disease onset. In T1D patients, circulating IgG memory B cells specific for IL-2 or insulin are present at similar frequencies. Anti-IL-2 autoantibodies cloned from T1D patients demonstrate clonality, a high degree of somatic hypermutation and nanomolar affinities, indicating a germinal centre origin and underscoring the synergy between cognate autoreactive T and B cells leading to defective immune tolerance.

Suggested Citation

  • Louis Pérol & John M. Lindner & Pamela Caudana & Nicolas Gonzalo Nunez & Audrey Baeyens & Andrea Valle & Christine Sedlik & Delphine Loirat & Olivier Boyer & Alain Créange & José Laurent Cohen & Ute C, 2016. "Loss of immune tolerance to IL-2 in type 1 diabetes," Nature Communications, Nature, vol. 7(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13027
    DOI: 10.1038/ncomms13027
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