[Study on the role of Th17 cells in the islet transplantation].
OBJECTIVE
To study the role of Th17 cells in the Immune rejection of islet transplantation, explore the feasibility of immune tolerance of islet transplantation induced by the combination applying of IL-23R antibody and Anti-CD154mAb.


METHODS
The in vitro experiments were divided into 5 groups: Blank control group, SD rat islet cells were cultured alone; A group, co-culture of rat pancreatic islet cells and lymphocytes, without IL-23R antibodies; B, C, D groups, co-culture of rat pancreatic islet cells and lymphocytes, respectively with IL-23R antibodies 0.1 microg/mL, 0.5 microg/mL, 1.0 microg/mL. Cells were harvested for Acridine orange (AO)/propidium iodide (PD) fluorescence staining, insulin and glucagon staining and glucose-stimulated insulin secretion test. The in vivo experiments (the purified islet to be transplanted under the left kidney capsule of the mice) were divided into four groups: Control group, BABL/c mice were transplanted with islets of SD rats with no treatments, IL-23R antibody (200 microg) treatment alone, anti-CD154mAb (200 microg) treatment alone and a combination of both. The blood glucose of the transplanted mice were monitored. The kidney of islet grafts were sliced for HE staining and insulin and glucagon immunohistochemical detection.


RESULTS
Three days after mixed cultivation, the glucose stimulation index was 3.66 +/- 0.10 in blank control group, which was higher than that of other groups. Stimulation index of D group was 1.95 +/- 0.75, which was significantly higher than that of other groups. The functional graft survival of all experimental groups were significantly better than that of control group as demonstrated by immunohistochemical staining of insulin and glucagon, as well as in vitro and in vivo experiments. After three days of islet transplantation, the blood glucose of control group was higher than that of experimental groups, but no significant difference was observed among experimental groups.


CONCLUSIONS
Th17 cells were involved in the islet transplant rejection. The expression of IL-17 could be considerably reduced through the block of the IL-23R, the effect of the block had a positive correlation in a dose-dependent manner. The combination of Anti-CD154 mAb and IL-23R antibody could prevent the acute rejection to some extent. However, there's no significant difference compared with the Anti-CD154mAb alone.
Xiong
Jun-Jie
JJ
Department of Hepatopancreatobiliary, West China Hospital, Sichuan University, Chengdu 610041, China.
Lu
Hui-Min
HM
Du
Xiao-Jiong
XJ
Ke
Neng-Wen
NW
Hu
Wei-Ming
WM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D023201:CD40 Ligand / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D020381:Interleukin-17 / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin; D023201:CD40 Ligand