Effect of corneal nerve ablation on immune tolerance induced by corneal allografts, oral immunization, or anterior chamber injection of antigens

Juan Mo, Sudha Neelam, Jessamee Mellon, Joseph R. Brown, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

PURPOSE. Severing corneal nerves during corneal transplantation does not affect first corneal transplants, but abolishes immune privilege of subsequent corneal allografts. This abrogation of immune privilege is attributable to the disabling of T regulatory cells (T regs) induced by corneal transplantation. The goal of this study was to determine if severing corneal nerves induces the development of contrasuppressor (CS) cells, which disable T regs that impair other forms of immune tolerance. METHODS. Effect of corneal nerve ablation on immune tolerance was assessed in four forms of immune tolerance: anterior chamber-associated immune deviation (ACAID); oral tolerance; corneal transplantation, and intravenously (IV) induced immune tolerance. T regulatory cell activity was assessed by adoptive transfer and by local adoptive transfer (LAT) of suppression assays. RESULTS. Corneal nerve ablation prevented ACAID and oral tolerance, but did not affect IVinduced immune tolerance. Contrasuppressor cells blocked the action of T regs that were generated by anterior chamber injection, oral tolerance, or orthotopic corneal transplantation. The neuropeptide substance P (SP) was crucial for contrasuppressor activity as CS cells could not be induced in SP-/- mice and the SP receptor inhibitor, Spantide II, prevented the expression of CS cell activity in vivo. Contrasuppressor cells expressed CD11c surface marker that identifies dendritic cells (DC). CONCLUSIONS. The loss of immune privilege produced by corneal nerve ablation following corneal transplantation extends beyond the eye and also affects immune tolerance induced through mucosal surfaces and appears to be mediated by a novel cell population of CD11cþ CS cells that disables T regs.

Original languageEnglish (US)
Pages (from-to)137-148
Number of pages12
JournalInvestigative Ophthalmology and Visual Science
Volume58
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Anterior chamber
  • Cornea
  • Immune privilege
  • Keratoplasty
  • Mucosal tolerance
  • T regs
  • Transplantation

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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