1. Complement C3 deficiency prevent against the onset of streptozotocin-induced autoimmune diabetes involving expansion of regulatory T cells
- Author
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Gao, Xiaogang, Liu, Huanhai, Ding, Guoshan, Wang, Zhengxin, Fu, Hong, Ni, Zhijia, Ma, Jun, Liu, Fang, and Fu, Zhiren
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COMPLEMENT deficiency (Immunology) , *STREPTOZOTOCIN , *DIABETES , *T cells , *AUTOIMMUNE diseases , *IMMUNOLOGICAL tolerance , *TRANSFORMING growth factors , *CELL proliferation - Abstract
Abstract: Recent studies have demonstrated that complement contributes to the development of autoimmune diabetes. However, the mechanisms remain unknown. Herein, using a model of streptozotocin (STZ)-induced diabetes, we found the presence of immune tolerance to self islet in complement C3-deficient mice after STZ. Higher number of CD4+CD25+ regulatory T cells (Tregs) with characteristics of expressing Foxp3 was observed in C3−/− mice. These C3−/− Tregs exhibited enhanced suppressive capacity to effector cell proliferation. The central role of Tregs was further evidenced by that depleting these cells using anti-CD25 antibody dramatically abrogated the preventive effects of C3 deficiency on STZ-induced diabetes. Importantly, transforming growth factor-β (TGF-β) was a key factor for Treg-mediated immune suppression as blocking TGF-β activity reversed suppressive capacity of Tregs in vitro and diabetes-resistant effects of C3 deficiency in vivo. These findings suggest that resistance to overt diabetes in STZ-treated C3−/− mice involves a population of Tregs in TGF-β-dependent manner. [Copyright &y& Elsevier]
- Published
- 2011
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