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Clin Immunol. 2014 Apr;151(2):114-26. doi: 10.1016/j.clim.2014.02.003. Epub 2014 Feb 19.

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

Author information

1
UPMC Université Paris 06, Sorbonne Universités, UMR 7211, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; CNRS, UMR 7211, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; AP-HP, Pitié-Salpêtrière hospital, Clinical Investigation Center in Biotherapy, F-75651 Paris, France.
2
Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain.
3
Center of Animal Biotechnology and Gene Therapy, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), 08036 Barcelona, Spain; Department of Anatomy and Animal Health, School of Veterinary Medicine, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
4
UPMC Université Paris 06, Sorbonne Universités, UMR 7211, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; CNRS, UMR 7211, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France.
5
Veterinary and Agrochemical Research Center (CODA-CERVA), 1180 Brussels, Belgium.
6
UPMC Université Paris 06, Sorbonne Universités, UMR 7211, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; CNRS, UMR 7211, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; INSERM, UMR_S 959, Immunology-Immunopathology-Immunotherapy (I3), F-75005 Paris, France; AP-HP, Pitié-Salpêtrière hospital, Clinical Investigation Center in Biotherapy, F-75651 Paris, France. Electronic address: david.klatzmann@umpc.fr.

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.

KEYWORDS:

Autoimmunity; Cancer; Infection; Inflammation; Maternal–fetal tolerance

PMID:
24576619
DOI:
10.1016/j.clim.2014.02.003
[Indexed for MEDLINE]

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