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Sustained stimulation and expansion of Tregs by IL2 control autoimmunity without impairing immune responses to infection, vaccination and cancer.
- Source :
-
Clinical immunology (Orlando, Fla.) [Clin Immunol] 2014 Apr; Vol. 151 (2), pp. 114-26. Date of Electronic Publication: 2014 Feb 19. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Female
Gene Expression Regulation immunology
Gene Transfer Techniques
HEK293 Cells
Humans
Interleukin-2 adverse effects
Lymphocyte Activation drug effects
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Time Factors
Autoimmunity immunology
Infections immunology
Interleukin-2 metabolism
Neoplasms immunology
T-Lymphocytes, Regulatory physiology
Vaccination
Subjects
Details
- Language :
- English
- ISSN :
- 1521-7035
- Volume :
- 151
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Clinical immunology (Orlando, Fla.)
- Publication Type :
- Academic Journal
- Accession number :
- 24576619
- Full Text :
- https://doi.org/10.1016/j.clim.2014.02.003