Abstract
Purpose: :
We found that γΔ T cells migrate into corneal epithelium in response to epithelial wounding, and healing and inflammation are significantly reduced in TCRΔ-/- mice (Am. J. Pathol 171:838-845, 2007). The current work is to define the contribution of Intercellular Adhesion Molecule-1 (ICAM-1) to corneal wound healing and γΔ T cell migration into the epithelium.
Methods: :
Limbal and paralimbal corneal epithelium was analyzed by qrtPCR, electron microscopy, and immunocytology at various time points after central corneal epithelial abrasion in female wildtype, ICAM-1-/- and P-selectin-/- C57BL/6 mice.
Results: :
Epithelial ICAM-1 mRNA was low at baseline, increased 26 fold at 3 hrs after abrasion, and returned to basal levels at 18 hrs. Re-epithelialization and epithelial cell division were significantly reduced (~50% at 18 hrs, p<0.01) after abrasion in ICAM-1-/- mice versus wild type, and at 96 hrs, recovery of epithelial thickness was only 66% (p<0.01) of wild type. ICAM-1-/- mice had 50.9% (p<0.01) fewer γΔ T cells resident in the limbus at baseline and failed to show significant changes in their number following abrasion. In contrast, wildtype mice had a 40% reduction of these cells at 3 hrs after abrasion followed by a ~5 fold increase at 24 hrs. Anti-ICAM-1 blocking antibody in wild type mice reduced the number of epithelial γΔ T cells to a number comparable to ICAM-1-/- mice. P-selectin-/- mice exhibited normal γΔ T cell kinetics in the epithelium following abrasion, and control antibodies failed to alter normal kinetics.
Keywords: cornea: epithelium • wound healing • inflammation