ZnT8107-115/HLA-A2 dimers attenuate the severity of diabetes by inducing CD8+ T cell tolerance.
Recent studies demonstrated that activated CD8+ T cells contributed to the development of T1D, and Zinc Transporter 8 (ZnT8) has emerged as a target of autoreactive T cells in human T1D in recent years. In the previous work, we identified that ZnT8107-115peptide as a candidate to generate CD8+ T cells and induce diabetes in mice. In addition, MHC-peptide complexes that interact with autoreactive T cells can induce immune tolerance. In the current study, we constructed ZnT8107-115/HLA-A2 dimers, and utilized them to immunize diabetes mice. The proliferation, cytotoxicity, and inflammatory cytokine of CD8+ T were analyzed, and the incidence and severity of diabetes were detected. We found that ZnT8107-115/HLA-A2 dimers inhibited proliferation, cytotoxicity, and inflammatory cytokine of CD8+ T. Additionally, ZnT8107-115/HLA-A2 dimers ameliorated the incidence and severity of diabetes mice. Our findings suggested that ZnT8107-115/HLA-A2 dimers abrogate pathogenic CD8+ T cells in diabetes, and the strategies represented promising way in T1D and other autoimmune diseases.
Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, Shangdong 276000, China.
Min
M
Zhang
Department of Nephrology, Linyi People's Hospital, Linyi, Shangdong 276000, China.
Zhongqi
Z
Zhou
Department of General Surgery, Linyi People's Hospital, Linyi, Shangdong 276000, China.
Jinguang
J
Wang
Department of Endocrinology, The Third People's Hospital of Linyi, Linyi, Shangdong 276000, China. Electronic address: shufali@163.com.
Shufa
S
Li
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology; D016207:Cytokines / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology*; D019281:Dimerization; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology; D010455:Peptides / Q000276:immunology; D000075703:Zinc Transporter 8 / Q000276:immunology*
D016207:Cytokines; D015789:HLA-A2 Antigen; D010455:Peptides; D000075703:Zinc Transporter 8
CD8+T cell; Diabetes; HLA-A2; Tolerance; ZnT8