B7-H4 transfection prolongs beta-cell graft survival.
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 beta-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-gamma-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-gamma 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 beta-cell graft survival.
Yuan
Chun-Lei
CL
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xu
Jun-Fa
JF
Tong
Jing
J
Yang
Heng
H
He
Feng-Rong
FR
Gong
Quan
Q
Xiong
Ping
P
Duan
Lihua
L
Fang
Min
M
Tan
Zheng
Z
Xu
Yong
Y
Chen
Yi-Fa
YF
Zheng
Fang
F
Gong
Fei-Li
FL
D000818:Animals; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000601:surgery*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000276:immunology / Q000378:metabolism; D007165:Immunosuppression Therapy / Q000379:methods*; D050417:Insulin-Secreting Cells / Q000276:immunology / Q000637:transplantation*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014162:Transfection; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
D018122:B7-1 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475824:Vtcn1 protein, mouse; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D007371:Interferon-gamma