ICAM-1 Is Necessary for Epithelial Recruitment of γδ T Cells and Efficient Corneal Wound Healing

Wound healing and inflammation are both significantly reduced in mice that lack gamma delta T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in gamma delta T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epithelial gamma delta T cells at 24 hours after epithelial abrasion. ICAM-1(-/-) mice had 50.9% (P < 0.01) fewer gamma delta T cells resident in unwounded corneal epithelium, which failed to increase in response to epithelial abrasion. Anti-ICAM-1 blocking antibody in wild-type mice reduced epithelial gamma delta T cells to a number comparable to that of ICAM-1(-/-) m mice, and mice deficient in lymphocyte function-associated antigen-1 (CD11a/CD18), a principal leukocyte receptor for ICAM-1, exhibited a 48% reduction (P < 0.01) in peak epithelial gamma delta T cells. Re-epithelialization and epithelial cell division were both significantly reduced (similar to 50% at 18 hours, P < 0.01) after abrasion in ICAM-1(-/-) mice versus wildtype, and at 96 hours, recovery of epithelial thickness was only 66% (P < 0.01) of wild-type. ICAM-1 expression by corneal epithelium in response to epithelial abrasion appears to be critical for accumulation of gamma delta T cells in the epithelium, and deficiency of ICAM-1 significantly delays wound healing. Since gamma delta T cells are necessary for efficient epithelial wound healing, ICAM-1 may contribute to wound healing by facilitating gamma delta T cell migration into the corneal epithelium. (Am J Pathol 2009, 175:571-579, DOI: 10.2353/ajpath.2009.090112)