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Title: Gamma delta T Cells Are Necessary for Platelet and Neutrophil Accumulation in Limbal Vessels and Efficient Epithelial Repair after Corneal Abrasion

Author
item LI, ZHIJIE - BAYLOR COLLEGE OF MED
item BURNS, ALAN - BAYLOR COLLEGE OF MED
item RUMBAUT, ROLANDO - BAYLOR COLLEGE OF MED
item Smith, Wayne

Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/11/2007
Publication Date: 9/1/2007
Citation: Li, Z., Burns, A., Rumbaut, R., Smith, W.C. 2007. Gamma delta T cells are necessary for platelet and neutrophil accumulation in limbal vessels and efficient epithelial repair after corneal abrasion. American Journal of Pathology. 171:838-845.

Interpretive Summary: This study uses an animal model of inflammation that allows direct visualization of cells in tissue since the tissue used (the cornea) is clear, allowing easy examination of cells using the light and fluorescent microscope. We investigated the importance of one class of white blood cells (called gamma delta T cells) in inflammation by studying inflammation in mice that were engineered to be deficient in this class of white blood cells. The results show that inflammation is markedly reduced in these mice. We also studied the effect of giving normal mice antibodies that block the function of this class of white blood cells, and found the same reduction in inflammation as seen in the deficient mice. The significance of this work relates to our current investigations to be published in the near future that gamma delta T cells are also important in the fat tissue inflammation in diet-induced obesity. It is important to find if there are differences in how gamma delta T cells work in fat tissue and in other tissue.

Technical Abstract: Corneal epithelial abrasion in C57BL/6 mice induces an inflammatory response, with peak accumulation of neutrophils in the corneal stroma within 12 hours. Platelets localize in the limbal vessels throughout the same time course as neutrophils and contribute to wound healing because antibody-dependent depletion of platelets retards epithelial division and wound closure. In the present study, T cells in the limbal epithelium were found to predominantly express the gamma delta T-cell receptor (TCR). Corneal abrasion in wild-type, CD11a(-/-), and P-sel(-/-) mice increased the numbers of gamma delta T cells in the limbal and peripheral corneal epithelium and in the corneal stroma adjacent to the limbal blood vessels. Intercellular adhesion molecule (ICAM)-1(-/-) mice exhibited a reduction in gamma delta T-cell accumulation. TCRdelta(-/-) mice exhibited reduced inflammation and delayed epithelial wound healing as evidenced by delayed wound closure, reduced epithelial cell division, reduced neutrophil infiltration, and reduced epithelial cell density at 96 hours after wounding. TCRdelta(-/-) mice also exhibited >60% reduction in platelet localization in the limbus despite similar platelet counts and platelet function assessed with an in vivo thrombosis model. These results are consistent with the conclusion that gamma delta T cells are necessary for efficient inflammation, platelet localization in the limbus, and epithelial wound healing after corneal abrasion.