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Juan Mo, Jessamee Mellon, Jerry Y Niederkorn; Effect of severing corneal nerves on the induction of immune tolerance during corneal transplantation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1444. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The severing of corneal nerves that occurs during orthotopic corneal transplantation abolishes immune privilege for subsequent corneal allografts and prevents T regulatory cells (Tregs) from suppressing immune rejection of future corneal allografts. The goal of this study was to determine if severing corneal nerves affects other forms of immune tolerance.
Corneal nerves were severed by making circular incisions (= trephining) in the corneas of BALB/c mice. Other groups of BALB/c mice, were either injected i.v. with substance P (SP) or received full thickness orthotopic corneal grafts from C57BL/6 mice. Four categories of immune tolerance were examined: a) anterior chamber-associated immune deviation (ACAID); b) intravenously induced immune tolerance; c) oral tolerance; and d) corneal transplantation-induced T regs.
ACAID was abrogated by circular incisions, injection of SP, or the application of an orthotopic corneal transplant. Oral administration of C57BL/6 alloantigens induced immune tolerance and the generation of alloantigen-specific Tregs (= oral tolerance). Like ACAID, either injection of SP or application of orthotopic corneal allografts prevented the induction of oral tolerance. Intravenously induced immune tolerance was not affected by SP, trephining or orthotopic corneal transplantation. Results from local adoptive transfer (LAT) assays indicated that severing corneal nerves promoted the generation of “contrasuppressor cells” (CS) that disabled T regs that are normally induced during ACAID. The CS were not antigen specific and functioned to block the action of Tregs that were generated by anterior chamber injection of alloantigens.
The results reveal that the first step of the corneal transplantation procedure (trephining) severs cornea nerves and exerts a systemic effect that prevents the induction and expression of immune tolerance induced through the anterior chamber or via mucosal routes (e.g. oral). However, immune tolerance induced by i.v. administration of antigens is unaffected by severing of corneal nerves. The loss of immune privilege that occurs following corneal transplantation extends beyond the eye and affects immune tolerance induced through mucosal surfaces and appears to be mediated by a novel cell population (contrasuppressor cell) that disables Tregs.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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