title: Exogenous IL-10 induces corneal transplantation immune tolerance by a mechanism associated with the altered Th1/Th2 cytokine ratio and the increased expression of TGF-β.
abstract: The aim of the present study was to examine the effect of exogenous IL-10 transfected rat dendritic cells (DCs) in corneal allografts. Rat lymphocyte separation medium and a cytokine induction method was used to extract and culture precursor cells of rat bone marrow-derived dendritic cells. A corneal transplant model was established, with Sprague-Dawley (SD) rats as the recipients and Wistar rats as the donors. Flow cytometry (FCM) was used to detect the expression of CD83, which indicates a mature dendritic cell, and a specific cell surface stimulatory molecule CD86. Western blot analysis was used to detect interleukin (IL)-10 protein expression and RT-PCR was used to detect cytokine IL-10, IL-2 and TGF-β mRNA expression in each group. Compared with the other groups, the survival time of corneal grafts in the IL-10-green fluorescent protein (GFP)-DC group was significantly prolonged and H&E staining demonstrated mild graft edema and inflammatory cell infiltration. There was a high expression of IL-10 and a low expression of the surface antigens, CD83 and CD86, with a lower proliferation of T lymphocytes in the IL-10-GFP-DC group. The expression of IL-10 and TGF-β in the IL-10-GFP-DC group was higher than that in the other groups, while the expression of IL-2 was lower. The transfection of the IL-10 gene inhibited dendritic cell maturation. IL-10 gene-modified immature dendritic cells (imDC) were able to inhibit corneal allograft rejection and induce immune tolerance to prolong the survival time of the corneal graft. The Th1/Th2 deviation and the high expression of TGF-β may lead to immune tolerance.
authors.affiliation: Department of Ophthalmology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Ophthalmology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Diao
authors.affiliation: Department of Ophthalmology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Liying
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology, First Hospital of Liaoning Medical College, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D003315:Cornea / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D016039:Corneal Transplantation; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007108:Immune Tolerance / Q000235:genetics; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010641:Phenotype; D051381:Rats; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D016753:Interleukin-10