title: Pretreatment of rapamycin before allogenic corneal transplant promotes graft survival through increasing CD4(+)CD25(+)Foxp3(+) regulatory T cells.
abstract: OBJECTIVE
  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.
  
  
  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: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors: Xin
authors: X
authors: Wang
authors: Wentao
authors: W
authors: Wang
authors: Jianjiang
authors: J
authors: Xu
authors: Jiaxu
authors: J
authors: Hong
authors: Qihua
authors: Q
authors: Le
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016039:Corneal Transplantation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000097:blood; D014184:Transplantation, Homologous
chemical_list: D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D020123:Sirolimus