The dose-related effect of monoclonal antibodies against adhesion molecules ICAM-1 and LFA-1 on peripheral nerve allograft rejection in a rat model

Donor-specific immunosuppression using anti-intercellular adhesion molecule-1 (ICAM-1) and anti-lymphocyte function-associated antigen-1 (LFA-1) has been shown to inhibit nerve allograft rejection without side effects. This dose-response study evaluated several dosing regimens using a 2-week course of three monoclonal antibodies (mAbs) against ICAM-1 and LFA-1 in combination on peripheral nerve allograft rejection in a rat model. Assessments of regeneration included walking track, electrophysiological, and histomorphologic analyses. Donor (ACI)-specific tolerance induction was assessed. Toxicity and mAb serum levels were monitored. At 18 weeks post engraftment, intermediate and high-dose groups were histologically indistinguishable from isograft controls, and superior to the untreated allograft group which demonstrated a significantly lower percent nerve tissue than all other groups. There were no differences in print length factor after 12 weeks or conduction velocity at sacrifice between any groups. Tolerance induction was not demonstrated. During mAb administration, animals in higher dose groups experienced temporary systemic side effects. This study demonstrated that a short course of mAb therapy directed against ICAM-1/LFA-1 inhibits rejection in rat peripheral nerve allografts by an unknown mechanism. The use of immune modulation in nerve transplantation may eliminate the need for systemic immunosuppression.