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*Autoimmune Diseases
The Journal of Immunology, 2005, 175: 4283-4291.
Copyright © 2005 by The American Association of Immunologists

Protection against Autoimmunity in Nonlymphopenic Hosts by CD4+CD25+ Regulatory T Cells Is Antigen-Specific and Requires IL-10 and TGF-{beta}1

Xiaopei Huang, Jiangao Zhu and Yiping Yang2

Departments of Medicine and Immunology, Duke University Medical Center, Durham, NC 27710

CD4+CD25+ regulatory T cells (TReg) play a critical role in the control of autoimmunity. However, little is known about how TReg suppress self-reactive T cells in vivo, thus limiting the development of TReg-based therapy for treating autoimmune diseases. This is in large part due to the dependency on a state of lymphopenia to demonstrate TReg-mediated suppression in vivo and the unknown Ag specificity of TReg in most experimental models. Using a nonlymphopenic model of autoimmune pneumonitis and TReg with known Ag specificity, in this study we demonstrated that these TReg can actively suppress activation of self-reactive T cells and protect mice from fatal autoimmune pneumonitis. The protection required TReg with the same Ag specificity as the self-reactive T cells and depended on IL-10 and TGF-{beta}. These results suggest that suppression of autoimmunity by TReg in vivo consists of multiple layers of regulation and advocate for a strategy involving Ag-specific TReg for treating organ-specific autoimmunity, because they do not cause generalized immune suppression.




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