B7-H4 transfection prolongs β-cell graft survival

• Published in: Transplant immunology 2009-07, Vol.21 (3), p.143-149
• Main Authors: Yuan, Chun-lei, Xu, Jun-fa, Tong, Jing, Yang, Heng, He, Feng-rong, Gong, Quan, Xiong, Ping, Duan, Lihua, Fang, Min, Tan, Zheng, Xu, Yong, Chen, Yi-fa, Zheng, Fang, Gong, Fei-li
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; B7-1 Antigen - genetics; B7-1 Antigen - immunology; B7-H4; Cell Line, Tumor; Diabetes Mellitus, Experimental - immunology; Diabetes Mellitus, Experimental - surgery; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - surgery; Graft Survival - genetics; Graft Survival - immunology; Green Fluorescent Proteins - immunology; Green Fluorescent Proteins - metabolism; Immunosuppression; Immunosuppression - methods; Insulin-Secreting Cells - immunology; Insulin-Secreting Cells - transplantation; Interferon-gamma - immunology; Interleukin-4 - immunology; Interleukin-4 - metabolism; Male; Mice; Mice, Inbred C57BL; Regulatory T cells; T-Lymphocytes, Regulatory - immunology; Transfection; V-Set Domain-Containing T-Cell Activation Inhibitor 1; β-cell transplantation
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2009.03.007

Abstract B7-H4, a recently discovered member of B7 family, can negatively regulate T cell responses. However, it is not clear whether B7-H4 negatively function in cell transplantation. In this study we investigated the immunosuppressive effect of B7-H4 on β-cell transplantation. An insulinoma cell line, NIT-1, transfected with B7-H4 (B7-H4-NIT) was established, and transplanted to diabetic C57BL/6 mice by intraperitoneal injection. Proliferation assay of splenocytes in vitro showed that B7-H4-NIT suppressed alloreactive T cell activation. The proportion of IFN-γ-producing cells in recipient spleen was significantly reduced and the number of Treg cells was upregulated in B7-H4-NIT group compared to the control, EGFP-NIT. The expression of mRNA coding IFN-γ was lower but that of IL-4 was higher in B7-H4-NIT transplanted recipients than in the control animals. The results of ELISA also revealed the same trends. Diabetic mice reached normalglycemic quickly and gained weight after transplantation of B7-H4-NIT. More importantly, the survival time for recipients transplanted with B7-H4-NIT cells was significantly longer than that with EGFP-NIT cells. These results indicate that B7-H4 transfection prolongs β-cell graft survival.