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Antonia Hildebrand, Thomas Reinhard, Johannes Schwartzkopff, Cornea - Immunology; Reduced expression of IL17 following rejection in baby rat keratoplasty. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2066.
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© ARVO (1962-2015); The Authors (2016-present)
An unexplained increase of graft rejections following keratoplasty is observed in very young patients (<1 year). Recently, IL17 -that is secreted by certain T cell subsets and that usually worsens the time course of an immune response- was described to be beneficial following keratoplasty. We hypothesized that T cells are crucial during this process and asked the question of an involvement of Th17 cells. In order to analyze this the baby rat keratoplasty model was used for T cell depletion experiments.
Orthotopic keratoplasty was performed between Fisher donor and Lewis recipient rats. All experiments were divided in two major groups: In group A, all recipients were 3 weeks-of-age and were either treated with a T cell-depleting or an isotypic antibody for one week. Group B contained untreated recipients only, that were either 3 or 10 weeks old. Corneal grafts were monitored clinically until rejection occurred but no longer than 35 days postoperatively. T cell-depletion was monitored by FACS. Lymph nodes and cornea were analyzed by qPCR for IL17-, IL6-, TGFβ-, and RORγt-mRNA-levels. Protein expression of IL17 was tested by intracellular FACS staining.
Group A: T cell depletion abrogated corneal graft rejection. Even after the T cell-pool had recovered no delayed onset of rejection episodes was observed. After complete T cell-recovery, mRNA of IL-6, TGFβ, IL17 and RORγt were increased in draining lymph nodes of initially T cell-depleted recipients compared to isotype controls. At the same time increased mRNA-levels for IL17 and RORγt were found in grafts of R73-treated animals. Group B: Independently of recipient age, IL17 mRNA-levels were decreased in draining lymph nodes of undepleted transplanted compared to naïve rats. This was confirmed by FACS where decreased numbers of CD4+IL17+ T cells were also detected.
Our results demonstrate that T cells are crucial during corneal graft rejection in baby rats. Despite complete T cell-recovery, no rejection occurs at a later time point in these animals. This is accompanied by increased IL17-mRNA-levels, that are otherwise reduced in untreated recipients of a corneal graft. We therefore speculate, that IL17 influences the time course of rejection following keratoplasty in baby rats.
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