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Li S.,Linyi Peoples Hospital | Li H.,The First Municipal Hospital of Guiyang City | Chen B.,Chongqing Medical University | Lu D.,Chongqing Medical University | And 4 more authors.
Vaccine | Year: 2013

Numerous evidences demonstrated that type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8+ T cells play an important role in the development of T1D. Zinc Transporter 8 (ZnT8) has emerged in recent years as a target of disease-associated autoreactive T cells in human T1D. However, ZnT8-associated CTL specific-peptides have not been identified. In this study, we predicted and identified HLA-A*0201-restricted cytotoxic T lymphocyte (CTL) epitopes derived from ZnT8, and utilized it to immunize HLA-A2.1/Kb transgenic (Tg) mice. The results demonstrated that peptides of ZnT8 containing residues 107-115, 115-123 and 145-153 could elicit specific CTLs in vitro, and induce diabetes in mice. The results suggest that these specific peptides are novel HLA-A*0201-restricted CTL epitopes, and could have therapeutic potential in preventing of T1D disease. © 2012 Elsevier Ltd. Source


Li S.,The First Municipal Hospital of Guiyang City | Zhang M.,Zhonghua Community Healthy Care Center | Xiang F.,The First Municipal Hospital of Guiyang City | Zhao J.,The First Municipal Hospital of Guiyang City | And 2 more authors.
Vaccine | Year: 2011

Numerous evidence demonstrate Type 1 diabetes (T1D) is due to a loss of immune tolerance to islet antigens, and CD8 + T cells play an important role in the development of T1D in NOD mice. The novel coinhibitory receptor BTLA may have a regulatory role in maintaining peripheral tolerance, however, its role in autoimmune diabetes is unknown. To explore whether the generation of tolerance aiming at BTLA will help therapeutic intervention in T1D, the NOD mice were treated with genetically modified dendritic cells (DCs) expressing BTLA. The results demonstrated that transfer of modified DCs significantly induced CD8 + T cell tolerance and attenuated the severity of diabetes. The findings suggest that genetically modified DC therapies enhancing the BTLA negative cosignal may prove valuable in treating T1D and other autoimmune diseases. © 2011 Elsevier Ltd. Source

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