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

6 Citations (Scopus)

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

Fingerprint

Immune Tolerance
Anterior Chamber
Allografts
Corneal Transplantation
Immunization
Antigens
Injections
Regulatory T-Lymphocytes
Adoptive Transfer
Substance P
Neurokinin-1 Receptors
Neuropeptides
Dendritic Cells
Transplants
Population

Keywords

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

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Effect of corneal nerve ablation on immune tolerance induced by corneal allografts, oral immunization, or anterior chamber injection of antigens. / Mo, Juan; Neelam, Sudha; Mellon, Jessamee; Brown, Joseph R.; Niederkorn, Jerry Y.

In: Investigative Ophthalmology and Visual Science, Vol. 58, No. 1, 01.01.2017, p. 137-148.

Research output: Contribution to journalArticle

@article{b42f8a57097e484aa15eb686ea638ebc,
title = "Effect of corneal nerve ablation on immune tolerance induced by corneal allografts, oral immunization, or anterior chamber injection of antigens",
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 CD11c{\th} CS cells that disables T regs.",
keywords = "Anterior chamber, Cornea, Immune privilege, Keratoplasty, Mucosal tolerance, T regs, Transplantation",
author = "Juan Mo and Sudha Neelam and Jessamee Mellon and Brown, {Joseph R.} and Niederkorn, {Jerry Y.}",
year = "2017",
month = "1",
day = "1",
doi = "10.1167/iovs.16-20601",
language = "English (US)",
volume = "58",
pages = "137--148",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "1",

}

TY - JOUR

T1 - Effect of corneal nerve ablation on immune tolerance induced by corneal allografts, oral immunization, or anterior chamber injection of antigens

AU - Mo, Juan

AU - Neelam, Sudha

AU - Mellon, Jessamee

AU - Brown, Joseph R.

AU - Niederkorn, Jerry Y.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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.

AB - 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.

KW - Anterior chamber

KW - Cornea

KW - Immune privilege

KW - Keratoplasty

KW - Mucosal tolerance

KW - T regs

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=85009508690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009508690&partnerID=8YFLogxK

U2 - 10.1167/iovs.16-20601

DO - 10.1167/iovs.16-20601

M3 - Article

C2 - 28114571

AN - SCOPUS:85009508690

VL - 58

SP - 137

EP - 148

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 1

ER -