Expansion of regulatory T cells via IL-2/anti-IL-2 mAb complexes suppresses experimental myasthenia
Ruolan Liu, Qinghua Zhou, Antonio La Cava, Denise I Campagnolo, Luc Van Kaer, Fu-Dong Shi, Ruolan Liu, Qinghua Zhou, Antonio La Cava, Denise I Campagnolo, Luc Van Kaer, Fu-Dong Shi
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.
Conflict of interest statement
Conflict of interest: The authors declare no financial or commercial conflict of interest.
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Source: PubMed