[Effect of anti-ICOS monoclonal antibody combined with low-dose CsA on chronic rejection of heart grafts in rats].
OBJECTIVE
To evaluate the effect of anti-inducible costimulator monoclonal antibody (anti-ICOS-Ab) combined with low-dose cyclosporine (CsA) on the survival quality and chronic rejection of heart allografts in rats.


METHODS
The rats' heterotopic cardiac transplantation model was established by Ono's method. The recipient rats were randomly divided into an isotransplantation control group and an allotransplantation experiment group. The experiment group was re-classified into a placebo group, a normal-dose CsA group, an anti-ICOS-Ab group, a low-dose CsA group, and an anti-ICOS-Ab combined with low-dose CsA group. The survival time of grafts was monitored. The cardiac grafts were harvested for histological analysis. Flow cytometric analysis was employed to detect the population of CD25+CD4+ in peripheral lymphocytes from recipients with a long-term surviving graft.


RESULTS
The survival time of the cardiac allografts in CsA-treated groups was significantly longer than that in placebo group (P<0.05). The survival time of the cardiac allografts in anti-ICOS-Ab combined with low-dose CsA group was significantly longer than that in low dose CsA-treated group (P<0.05). There was no significant difference in the survival time of the cardiac grafts between the anti-ICOS-Ab group and the placebo group (P>0.05). Compared with the normal-dose CsA group, the chronic rejection lesions of the anti-ICOS-Ab combined with low-dose CsA treatment group significantly were alleviated in the long-term survival grafts, and the proportion of CD4+CD25+ regulatory T cell increased in peripheral blood.


CONCLUSIONS
The anti-ICOS-Ab combined with low-dose CsA can prolong the survival of cardiac allografts and alleviate the chronic rejection significantly. The high expression level of CD4+CD25+ regulatory T cell is beneficial to the long-term survival of grafts.
Zhao
Yu-jun
YJ
Xiangya Transplantation Medical Academy, Third Xiangya Hospital, Central South University, Research Center of Transplantation Medicine Engineering and Technology, China Ministry of Health, Changsha 410013, China. zyjdoc@yahoo.com.cn
Huang
Zu-fa
ZF
Cheng
Ke
K
Zhu
Shai-hong
SH
Ye
Qi-fa
QF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000188:drug therapy*; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects*; D060889:Inducible T-Cell Co-Stimulator Protein; D011897:Random Allocation; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D060889:Inducible T-Cell Co-Stimulator Protein; D016572:Cyclosporine