IL-7 receptor blockade reverses autoimmune diabetes by promoting inhibition of effector/memory T cells

Cristina Penaranda, Wilson Kuswanto, Jerry Hofmann, Rupert Kenefeck, Partheepan Narendran, Lucy S K Walker, Jeffrey A Bluestone, Abul K Abbas, Hans Dooms

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)


To protect the organism against autoimmunity, self-reactive effector/memory T cells (T(E/M)) are controlled by cell-intrinsic and -extrinsic regulatory mechanisms. However, how some T(E/M) cells escape regulation and cause autoimmune disease is currently not understood. Here we show that blocking IL-7 receptor-α (IL-7Rα) with monoclonal antibodies in nonobese diabetic (NOD) mice prevented autoimmune diabetes and, importantly, reversed disease in new-onset diabetic mice. Surprisingly, IL-7-deprived diabetogenic T(E/M) cells remained present in the treated animals but showed increased expression of the inhibitory receptor Programmed Death 1 (PD-1) and reduced IFN-γ production. Conversely, IL-7 suppressed PD-1 expression on activated T cells in vitro. Adoptive transfer experiments revealed that T(E/M) cells from anti-IL-7Rα-treated mice had lost their pathogenic potential, indicating that absence of IL-7 signals induces cell-intrinsic tolerance. In addition to this mechanism, IL-7Rα blockade altered the balance of regulatory T cells and T(E/M) cells, hence promoting cell-extrinsic regulation and further increasing the threshold for diabetogenic T-cell activation. Our data demonstrate that IL-7 contributes to the pathogenesis of autoimmune diabetes by enabling T(E/M) cells to remain in a functionally competent state and suggest IL-7Rα blockade as a therapy for established T-cell-dependent autoimmune diseases.
Original languageEnglish
Pages (from-to)12668-73
Number of pages6
JournalNational Academy of Sciences. Proceedings
Issue number31
Publication statusPublished - 31 Jul 2012


  • Adoptive Transfer
  • Animals
  • Antigens, Differentiation
  • Diabetes Mellitus, Type 1
  • Female
  • Immune Tolerance
  • Immunologic Memory
  • Interferon-gamma
  • Interleukin-7
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred NOD
  • Receptors, Interleukin-7
  • Signal Transduction
  • T-Lymphocytes


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