The immunosuppressive and protective ability of glucose-regulated protein 78 for improvement of alloimmunity in beta cell transplantation.
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.
Wang
M
M
Department of Immunology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
Wang
P
P
Liu
Y Q
YQ
Peng
J L
JL
Zhao
X P
XP
Wu
S
S
He
F R
FR
Wen
X
X
Li
Y
Y
Shen
G X
GX
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology / Q000628:therapy*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D007165:Immunosuppression Therapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000276:immunology* / Q000378:metabolism; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D001786:Blood Glucose; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D015847:Interleukin-4; D007371:Interferon-gamma