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Christian Jarsch, Laura Bredow, Yvonne Kern, Daniel Böhringer, Philipp Eberwein, Thomas Reinhard, Johannes Schwartzkopff; Subconjunctival Transfer of Regulatory T Cells Promotes Corneal Graft Survival. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1147.
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Naturally occurring CD4+CD25+FoxP3+ regulatory T cells (Treg) are known to be involved in the regulation of an immune reaction following keratoplasty. Because graft rejection has been shown to occur faster in baby rats, we hypothesized that this could be a consequence of an underdeveloped Treg-pool.
In vitro: All in vitro experiments were compared between 3- (young) and 10-week-old (old) rats. FoxP3 was analyzed by flow cytometry and rtPCR. Treg were isolated and tested for their inhibitory capacity on T cell proliferation. In vivo: Keratoplasty was performed between old Fisher donor and young Lewis recipient rats. Subsequently, old syngeneic GFP+ Treg were adoptively transferred intravenously or subconjunctivally. Control animals received CD4+CD25- T cells. All transplants were monitored clinically until rejection occurred and cellular infiltration was analyzed histologically. Transferred GFP+ CD4+ T cells were followed in lymphatic tissues by flow cytometry.
No differences in amount or FoxP3-level of Treg was observed between old and young rats. Inhibitory capacity of Treg was independently of their age. Systemic adoptive transfer of Treg did not affect graft survival, whereas subconjunctival injection of Treg improved survival times significantly when compared to control animals (p<0.01). All surviving Treg-treated grafts showed a reduced immunological infiltration. Locally transferred GFP+ CD4+ T cells migrated to the spleen but not to lymphnodes.
Increasing Treg-numbers in young rats by intravenous tranfer does influence allograft survival following keratoplasty. However, subconjunctival injection of Treg improves survival rates significantly. Naïve Treg seem to be primed following keratoplasty if transferred subconjunctivally. Thereby, they may achieve allo-specificity leading to regulation of graft rejection. Naïve Treg could thus be a new therapeutical approach following keratoplasty in infants or patients with elevated risk factors.
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