Protection against autoimmunity in nonlymphopenic hosts by CD4+ CD25+ regulatory T cells is antigen-specific and requires IL-10 and TGF-beta.
CD4+ CD25+ regulatory T cells (T(Reg)) play a critical role in the control of autoimmunity. However, little is known about how T(Reg) suppress self-reactive T cells in vivo, thus limiting the development of T(Reg)-based therapy for treating autoimmune diseases. This is in large part due to the dependency on a state of lymphopenia to demonstrate T(Reg)-mediated suppression in vivo and the unknown Ag specificity of T(Reg) in most experimental models. Using a nonlymphopenic model of autoimmune pneumonitis and T(Reg) with known Ag specificity, in this study we demonstrated that these T(Reg) can actively suppress activation of self-reactive T cells and protect mice from fatal autoimmune pneumonitis. The protection required T(Reg) 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 T(Reg) in vivo consists of multiple layers of regulation and advocate for a strategy involving Ag-specific T(Reg) for treating organ-specific autoimmunity, because they do not cause generalized immune suppression.
Huang
Xiaopei
X
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Zhu
Jiangao
J
Yang
Yiping
Y
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000401:mortality; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D016753:Interleukin-10 / Q000502:physiology*; D008231:Lymphopenia / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology / Q000401:mortality; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D016753:Interleukin-10