Induction of contrasuppressor cells and loss of immune privilege produced by corneal nerve ablation

Sudha Neelam, Jessamee Mellon, Amber Wilkerson, Jerry Y. Niederkorn

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

PURPOSE. Severing of corneal nerves in preparation of corneal transplantation abolishes immune privilege of subsequent corneal transplants placed into either eye: a phenomenon termed sympathetic loss of immune privilege (SLIP). SLIP is due to the disabling of T regulatory cells (Tregs) by CD11c+ contrasuppressor (CS) cells. This study characterized the induction, function, and manipulation of CS cell activity and the effect of these cells on Tregs induced by anterior chamber-associated immune deviation (ACAID). METHODS. CS cells were induced using a 2.0-mm trephine to score the corneal epithelium. CD11c+ CS cells were evaluated by adoptive transfer and by their capacity to disable CD8+ ACAID Tregs in local adoptive transfer (LAT) of suppression assays. CD11c+ cells were deleted from the ocular surface by subconjunctival injection of clodronate-containing liposomes. RESULTS. CD11c+ CS cell were radiosenstive and long lived. As few as 1000 CS cells blocked the suppressive activity of previously generated CD8+ ACAID Tregs, indicating that CS cells act at the efferent arm of the immune response. Depletion of resident CD11c+ cells at the ocular surface prevented the generation of CS cells. CONCLUSIONS. Corneal nerve injury that occurs during keratoplasty converts ocular surface CD11c+ cells into CS cells that block CD8+ Tregs, which are induced by introducing antigens into the anterior chamber (i.e., ACAID Tregs). Depletion of CD11c+ cells at the ocular surface prevents the generation of CS cells and may be a useful strategy for preventing SLIP and enhancing the survival of second corneal transplants.

Original languageEnglish (US)
Pages (from-to)4738
Number of pages1
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number11
DOIs
StatePublished - Sep 2018

Keywords

  • Anterior chamber
  • Contrasuppressor cells
  • Cornea
  • Immune privilege
  • Transplantation
  • Tregs

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Induction of contrasuppressor cells and loss of immune privilege produced by corneal nerve ablation'. Together they form a unique fingerprint.

Cite this