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S. Byeseda, A. R. Burns, C. W. Smith, Z. Li; ICAM-1 Is Necessary for Efficient Corneal Wound Healing and Recruitment of Gamma Delta T Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6294.
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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.
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.
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.
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