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  • Title: Pretreatment of rapamycin before allogenic corneal transplant promotes graft survival through increasing CD4(+)CD25(+)Foxp3(+) regulatory T cells.
    Author: Wang X, Wang W, Xu J, Hong J, Le Q.
    Journal: Exp Clin Transplant; 2013 Feb; 11(1):56-62. PubMed ID: 22769982.
    Abstract:
    OBJECTIVES: To evaluate the effect of rapamycin pretreatment before allogenic corneal transplant on CD4(+)CD25(+)Foxp3(+)T regulatory cells (Treg) in recipient mice, and analyze its correlation with graft survival. MATERIALS AND METHODS: Balb/c mice were intraperitoneally injected with rapamycin or control solution for 2 weeks. They then underwent a corneal transplant with C57/BL6 serving as the donor. Graft status was assessed twice a week. Recipient mice were killed 14 days after surgery, and the percentage of CD4(+)CD25(+)Foxp3(+)Treg in peripheral blood, spleen, and draining lymph nodes was analyzed by flow cytometry. Moreover, CD4(+)CD25(+)T cells in corneal grafts and conjunctiva were identified, and expression of Foxp3 mRNA in the grafts was tested. Additionally, the concentration of IL-10 and TGF-β1 in serum and aqueous humor was measured. RESULTS: Pretreatment of rapamycin significantly enhanced the percentage of CD4(+)CD25(+)Foxp3(+)Treg in peripheral blood and draining lymph nodes, preoperatively and postoperatively, which had significant negative correlation with graft opacity and neovascularization. Moreover, rapamycin pretreatment led to a larger number of CD4(+)CD25(+)T cells infiltrating in corneal grafts and conjunctiva, increased expression of Foxp3 mRNA in grafts, and elevated concentration of TGF-β1 in aqueous humor. CONCLUSIONS: Pretreatment with rapamycin for 14 days before an allogenic corneal transplant enhances the percentage of CD4(+)CD25(+)Foxp3(+)Treg cells in peripheral blood, draining lymph nodes, and grafts, thereby inhibiting graft rejection.
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