The role of cell adhesion molecules in allograft rejection after penetrating keratoplasty in mice. Clinical and immunohistochemical study.
BACKGROUND: It has been reported that adhesion molecules play an important role in immunological rejection after organ transplantation. In the present study, we examined the role of ICAM-1/ LFA-1 adhesion molecules in corneal allograft rejection and evaluated the immunological specificity of monoclonal antibodies (mAbs) in preventing allograft rejection in mice. METHODS: The allografted mice were intraperitoneally injected with 100 micrograms/day of the following mAbs: a control mAb, anti-ICAM-1 mAb, anti-LFA-1 mAb, or a mixture of anti-ICAM-1 and anti-LFA-1 mAbs from 1 day before to 7 days after surgery. The expression of ICAM-1 and LFA-1 molecules in the grafted cornea was studied immunohistochemically. The corneas from a syngeneic donor or a third-party strain were transplanted 4 weeks after the initial keratoplasty onto the mice treated with both anti-ICAM-1 and anti-LFA-1 mAbs. RESULTS: The allografts treated with anti-LFA-1 mAb alone or both anti-ICAM-1 and anti-LFA-1 mAbs remained transparent for more than 2 weeks, and the survival rate at 8 weeks was 40% in both groups. ICAM-1 was expressed on the mononuclear cells, keratocytes and endothelial cells in the allografts without treatment. The second corneal grafts syngeneic to the initial donor remained transparent at 2 weeks, whereas those from the third party were rejected. CONCLUSIONS: ICAM-1 and LFA-1 adhesion molecules play a crucial role in the pathophysiology of corneal transplant rejection. The immunosuppressive effects of anti-ICAM-1 and anti-LFA-1 mAbs are highly allospecific. The administration of mAbs to the adhesion molecules represents a new means of suppressing allograft rejection after penetrating keratoplasty.