The immunosuppressive and protective ability of glucose-regulated protein 78 for improvement of alloimmunity in beta cell transplantation |
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| Authors: | Wang M Wang P Liu Y Q Peng J L Zhao X P Wu S He F R Wen X Li Y Shen G X |
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| Affiliation: | Department of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. |
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| Abstract: | An insulinoma cell line, NIT-1, transfected with glucose-regulated protein 78 (GRP78) was established, namely NIT-GRP78, and used to study the immunosuppressive and protective ability of GRP78. In extended cytotoxic T lymphocyte (CTL) killing assay, NIT-1-primed lymphocytes were more cytotoxic in killing beta cells than NIT-GRP78-primed lymphocytes. Severe necrosis was observed only when the NIT-1-primed lymphocytes were cultured with NIT-1 beta cells, but not with NIT-GRP78 cells. In addition, an increase of interleukin (IL)-4 secretion from beta cell-primed splenocytes when GRP78 presence was observed in cytokine enzyme-linked immunosorbent assay (ELISA). Diabetic mice reached normoglycaemia promptly and gained weight after transplantation of either NIT-1 or NIT-GRP78 cells. However, the recipient mice transplanted with NIT-GRP78 cells lived much longer than those recipients transplanted with NIT-1 cells, which was due apparently to prolonged insulin production by the transplanted NIT-GRP78 cells. In fact, we observed a significant increase of insulin concentration after glucose stimulation of diabetic mice received NIT-GRP78 cells at day 7 post-transplantation. From the results we propose that GRP78 could have a dual function in both protecting NIT-1 cells from CTL-mediated lysis and stimulating a population of T helper 2 cells to down-regulate the immune response to the transplanted beta cells. |
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| Keywords: | β cell transplantation cytotoxic T cells glucose-regulated protein 78 immunosuppression |
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