Protective role for CD1d-reactive invariant natural killer T cells in cauterization-induced corneal inflammation

Invest Ophthalmol Vis Sci. 2008 Jan;49(1):105-12. doi: 10.1167/iovs.07-0284.

Abstract

Purpose: Corneal inflammation can be induced by various stimuli, such as chemical burns, trauma, and acute bacterial infection, and directly impairs visual acuity. Natural killer T (NKT) cells belong to a specialized population of leukocytes that coexpress the T-cell receptor and NK markers. This study examined the role of CD1d-reactive invariant NKT cells in cauterization-induced acute corneal inflammation.

Methods: The corneas of CD1d-knockout (KO) mice and Jalpha18-KO mice (both of which are NKT cell deficient) and control mice were cauterized with silver nitrate. Corneal edema and opacity were examined, and the phenotypes of the corneal-infiltrating cells were analyzed histologically at 24 hours and by flow cytometry at 96 hours. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression of vascular endothelial growth factor (VEGF), interferon (IFN)gamma, and tumor necrosis factor (TNF)alpha in the cauterized corneas.

Results: The CD1d-KO and Jalpha18-KO mice had significantly greater levels of corneal edema and opacity than did the control mice. Although the number of infiltrating cells was not significantly different at 96 hours, both groups of NKT cell-deficient mice demonstrated increased early neutrophil accumulation at 24 hours and early expression of VEGF, IFNgamma, and TNFalpha. There was no difference in the level of VEGF-induced corneal neovascularization.

Conclusions: NKT cells appear to regulate the early accumulation of neutrophils, protect the cornea from excessive inflammation, and maintain corneal clarity. However, in this study, they did not affect the corneal revascularization process induced by VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1 / metabolism*
  • Antigens, CD1d
  • Corneal Edema / metabolism
  • Corneal Edema / pathology
  • Corneal Edema / prevention & control
  • Corneal Opacity / metabolism
  • Corneal Opacity / pathology
  • Corneal Opacity / prevention & control
  • Female
  • Flow Cytometry
  • Interferon-gamma / genetics
  • Keratitis / chemically induced
  • Keratitis / metabolism
  • Keratitis / pathology
  • Keratitis / prevention & control*
  • Killer Cells, Natural / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / physiology
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Silver Nitrate / toxicity
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / genetics
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Antigens, CD1
  • Antigens, CD1d
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Interferon-gamma
  • Silver Nitrate