期刊
CLINICAL IMMUNOLOGY
卷 151, 期 2, 页码 114-126出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2014.02.003
关键词
Autoimmunity; Cancer; Infection; Inflammation; Maternal-fetal tolerarice
类别
资金
- Academie Nationale de Medecine
- Ministere de la Recherche
- Ministerio de Educacion, Cultura y Deporte
- Ministerio de Economia y Competitividad, Plan Nacional I + D+ I [SAF2011-24698]
- Generalitat de Catalunya, Spain [2009 SGR-224]
- CNRS
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 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. (C) 2014 Elsevier Inc. All rights reserved.
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