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Pretreatment of rapamycin before allogenic corneal transplant promotes graft survival through increasing CD4(+)CD25(+)Foxp3(+) regulatory T cells.
Exp Clin Transplant 2013; 11(1):56-62EC

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.

Authors+Show Affiliations

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22769982

Citation

Wang, Xin, et al. "Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4(+)CD25(+)Foxp3(+) Regulatory T Cells." Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation, vol. 11, no. 1, 2013, pp. 56-62.
Wang X, Wang W, Xu J, et al. Pretreatment of rapamycin before allogenic corneal transplant promotes graft survival through increasing CD4(+)CD25(+)Foxp3(+) regulatory T cells. Exp Clin Transplant. 2013;11(1):56-62.
Wang, X., Wang, W., Xu, J., Hong, J., & Le, Q. (2013). Pretreatment of rapamycin before allogenic corneal transplant promotes graft survival through increasing CD4(+)CD25(+)Foxp3(+) regulatory T cells. Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation, 11(1), pp. 56-62. doi:10.6002/ect.2012.0025.
Wang X, et al. Pretreatment of Rapamycin Before Allogenic Corneal Transplant Promotes Graft Survival Through Increasing CD4(+)CD25(+)Foxp3(+) Regulatory T Cells. Exp Clin Transplant. 2013;11(1):56-62. PubMed PMID: 22769982.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pretreatment of rapamycin before allogenic corneal transplant promotes graft survival through increasing CD4(+)CD25(+)Foxp3(+) regulatory T cells. AU - Wang,Xin, AU - Wang,Wentao, AU - Xu,Jianjiang, AU - Hong,Jiaxu, AU - Le,Qihua, Y1 - 2012/07/05/ PY - 2012/7/10/entrez PY - 2012/7/10/pubmed PY - 2013/8/10/medline SP - 56 EP - 62 JF - Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation JO - Exp Clin Transplant VL - 11 IS - 1 N2 - 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. SN - 2146-8427 UR - https://www.unboundmedicine.com/medline/citation/22769982/Pretreatment_of_rapamycin_before_allogenic_corneal_transplant_promotes_graft_survival_through_increasing_CD4_+_CD25_+_Foxp3_+__regulatory_T_cells_ L2 - http://www.ectrx.org/forms/ectrxcontentshow.php?year=2013&volume=11&issue=1&supplement=0&makale_no=0&spage_number=56&content_type=FULL TEXT DB - PRIME DP - Unbound Medicine ER -