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Qihua Le, Xin Wang, Wentao Wang, JianJiang Xu; Effect Of Rapamycin And IL-2 On Regulatory CD4+CD25+Foxp3+T Cells In Mice After Allogenic Penetrating Keratoplasty. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6178.
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To explore the effect of rapamycin and IL-2 on regulatory CD4+CD25+Foxp3+T cells (Treg) in recipient mice after allogenic penetrating keratoplasty, and analyze its correlation with the graft outcome.
Allogenic penetrating keratoplasty was performed from C57/BL6 to Balb/c mice. The treatment of rapamycin, IL-2, rapamycin+IL-2 (mixed group), and control solution was administered to recipient mice for 14 days after the surgery. The graft status was assessed twice a week. Apart from histological examination of eyeball, the percentage of CD4+CD25+Foxp3+Treg in the peripheral blood, spleen and draining lymph nodes was analyzed by flow cytometry. Moreover, the expression of Foxp3 mRNA in grafts was tested, and the concentration of IL-10 and TGF-β1 in serum and aqueous humor was measured.
The highest scores of graft neovascularization and opacity were found in control group, and the lowest ones were almost in mixed group. The percentage of CD4+CD25+Foxp3+Tregs in blood increased significantly in mice treated with either rapamycin or IL-2, and a synergistic effect was found in the mixed group. Concerning CD4+CD25+Foxp3+Tregs in either spleen or draining lymph nodes, the synergistic effects were likewise found in mixed group. The percentage of Tregs had significant negative correlation with graft neovascularization and opacity. Nevertheless, the concentration of both TGF-β1 and IL-10 in the serum and aqueous humor increased significantly in mice of IL-2, rapamycin, and mix group.
In vivo administration of rapamycin inhibited graft rejection after allogenic penetrating keratoplasty through expansion of CD4+CD25+Foxp3+Tregs. This effect could be amplified with the combination of IL-2.
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