Wound healing and inflammation are both significantly reduced in mice that lack ␥␦ T cells. Here, the role of epithelial intercellular adhesion molecule-1 (ICAM-1) in ␥␦ T cell migration in corneal wound healing was assessed. Wild-type mice had an approximate fivefold increase in epithelial ␥␦ T cells at 24 hours after epithelial abrasion. ICAM-1 ؊/؊ mice had 50.9% (P < 0.01) fewer ␥␦ 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 ␥␦ T cells to a number comparable to that of ICAM-1 ؊/؊ 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 ␥␦ T cells. Re-epithelialization and epithelial cell division were both significantly reduced (ϳ50% 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 ␥␦ T cells in the epithelium , and deficiency of ICAM-1 significantly delays wound healing. Since ␥␦ T cells are necessary for efficient epithelial wound healing , ICAM-1 may contribute to wound healing by facilitating ␥␦ T cell migration into the corneal epithelium.

Corresponding Author: (Same for reprint requests), Oluyinka Olutoye, MB, ChB, PhD, Division of Pediatric Surgery, Baylor College of Medicine, 6621 Fannin St, CC650.00, Houston, TX 77030-2399, Tel: (832) Fax: (832) 825-3141, oolutoye@bcm.tmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Presented at the 39 th Annual Meeting of the Canadian Association of Pediatric Surgeons. Winner of the best basic science paper presentation (ANG). NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptIntroduction-GCSF is commonly employed for the treatment of chemotherapy-induced neutropenia. Despite high-dose intensive chemotherapy for advanced stage neuroblastoma, the survival rate remains poor. GCSF therapy is quite common in these children, thus we questioned its effect on neuroblastoma cells. We hypothesized that exogenous GCSF stimulates the proliferation and invasive character of neuroblastoma cells.

We found that γδ T cells migrate into murine corneal epithelium in response to epithelial wounding, and wound healing and inflammation are significantly reduced in TCRδ −/− mice (Am. J. Pathol 171:838–845, 2007). The current work is to define mechanisms for migration of γδ T cells into corneal epithelium. Limbal and paralimbal corneal epithelium was collected at 0 and 3 hrs after central abrasion in female C57BL/6 mice for qrtPCR, and immunocytology. Results: ICAM‐1 mRNA was increased 26 fold at 3 hrs. Anti‐ICAM‐1 staining was negative at 0 hr, but strongly positive over the limbal and paralimbal epithelium at 3 hrs. γ/δ T cells increased at 3 hrs after injury, but ICAM‐1−/− mice failed to show an increase. Of 11 chemokine receptors probed, only CCR3 and CCR5 were significantly increased in wildtype mice at 3 hrs. mRNA for chemokines recognized by these receptors was significantly increased: CCL3 (MIP‐1α), CCL4 (MIP‐1β), CCL5 (RANTES) and CCL7 (MCP‐3). Further, CXCL10 (IP‐10) mRNA was also significantly increased. CXCL10 is known to attract some γδ T cells, but its receptor (CXCR3) was not evident here. Conclusion: The migration of γδ T cells into murine corneal epithelium in response to epithelial abrasion appears to depend on ICAM‐1 expression, and since CCR5 is reported on some γδ T cells, our observations suggest a mechanism for attraction into corneal epithelium.Source of research support: General Clinical Research Centers