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Eur J Immunol. 2010 Jun;40(6):1577-89. doi: 10.1002/eji.200939792.

Expansion of regulatory T cells via IL-2/anti-IL-2 mAb complexes suppresses experimental myasthenia.

Author information

1
Department of Neurology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA. Ruolan.Liu@chw.edu

Abstract

Human autoimmune diseases are often characterized by a relative deficiency in CD4(+)CD25(+) regulatory T cells (Treg). We therefore hypothesized that expansion of Treg can ameliorate autoimmune pathology. We tested this hypothesis in an experimental model for autoimmune myasthenia gravis (MG), a B-cell-mediated disease characterized by auto-Ab directed against the acetylcholine receptor within neuromuscular junctions. We showed that injection of immune complexes composed of the cytokine IL-2 and anti-IL-2 mAb (JES6-1A12) induced an effective and sustained expansion of Treg, via peripheral proliferation of CD4(+)CD25(+)Foxp3(+) cells and peripheral conversion of CD4(+)CD25(-)Foxp3(-) cells. The expanded Treg potently suppressed autoreactive T- and B-cell responses to acetylcholine receptor and attenuated the muscular weakness that is characteristic of MG. Thus, IL-2/anti-IL-2 mAb complexes can expand functional Treg in vivo, providing a potential clinical application of this modality for treatment of MG and other autoimmune disorders.

Comment in

PMID:
20352624
PMCID:
PMC3600978
DOI:
10.1002/eji.200939792
[Indexed for MEDLINE]
Free PMC Article

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