Sustained stimulation and expansion of Tregs by IL2 control autoimmunity without impairing immune responses to infection, vaccination and cancer

Guillaume Churlaud, Veronica Jimenez, Jesus Ruberte, Martin Amadoudji Zin, Gwladys Fourcade, Gaelle Gottrand, Estefania Casana, Benedicte Lambrecht, Bertrand Bellier, Eliane Piaggio, Fatima Bosch, David Klatzmann

Research output: Contribution to journalArticleResearchpeer-review

30 Citations (Scopus)

Abstract

Interleukin 2 (IL2) is the key cytokine supporting survival and function of regulatory T cells (Tregs). We recently reported that low-dose IL2 safely expands/stimulates Tregs and improves autoimmune conditions in humans. Further development of IL2 in autoimmune diseases will require chronic IL2 administration, which could affect beneficial effector immune responses regulated by Tregs. We used recombinant adeno-associated viral vector (rAAV)-mediated gene transfer to continuously release IL2 in mice and assessed its long-term effects on immune responses. A single rAAV-IL2 injection enabled sustained stimulation and expansion of Tregs without inducing Teff activation and prevented diabetes in NOD mice. After several weeks of IL2 production, mice responded normally to a viral challenge and to vaccination, and had pregnancies with offspring that developed normally. They showed no change in the occurrence and growth of chemically-induced tumors. Altogether, chronic low-dose IL2 treatment does not affect beneficial effector immune responses at doses that prevent autoimmune diabetes. © 2014 Elsevier Inc.
Original languageEnglish
Pages (from-to)114-126
JournalClinical Immunology
Volume151
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Autoimmunity
  • Cancer
  • Infection
  • Inflammation
  • Maternal-fetal tolerance

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