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Felix Bock, Alexander Steinkasserer, Claus Cursiefen, Elisabeth Zinser; Topical sCD83 Induces Graft Tolerance In High-risk Corneal Transplantation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6177.
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CD83 was shown to influence the maturation of dendritic cells leading to the induction of regulatory T cells. Purpose of this study was to investigate the effect of topical sCD83 on the outcome of high-risk corneal transplantation.
Using the model of high-risk keratoplasty in the mouse, sCD83 or sCD83 + 1-MT was applied systemically as well as eye drops. The graft outcome was graded weekly for 8 weeks. In addition, induction of regulatory T cells by dendritic cells was analysed by FACS analysis on CD4 and FoxP3.
Systemic treatment with sCD83 leads to significant improvement of graft survival after high risk (inflamed/vascularised) keratoplasty (p< 0.011). Using sCD83 as topical eye drops leads to an equal improvement (p<0.026). This effect can be diminished by the IDO (Indolamin-2,3-Dioxygenase) antagonist 1-MT (p< 0.388). sCD83 in combination with DCs let to an increase of FoxP3+ CD4+ T cells (control: 2.5%; sCD83: 6.42%), whereas sCD83 alone did not have an effect on the regulatory fraction of the T cell population.
Topical sCD83 has a beneficial effect on the graft survival after high risk transplantation. This effect seems to be mediated by the shift of mature DCs to semimature or regulatory DCs via interaction of sCD83 with IDO inducing an increased population of regulatory T cells in the host. Thereby sCD83 offers a new strategy to avoid graft rejection in high risk patients.
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