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 mol ecule-1 (ICAM-1) and anti-lymphocyte function-associated antigen-1 (LF A-1) has been shown to inhibit nerve allograft rejection without side effects. This dose-response study evaluated several dosing regimens us ing 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, elec trophysiological, and histomorphologic analyses. Donor (ACI)-specific tolerance induction was assessed. Toxicity and mAb serum levels were m onitored. At 18 weeks post engraftment, intermediate and high-dose gro ups were histologically indistinguishable from isograft controls, and superior td the untreated allograft group which demonstrated a signifi cantly lower percent nerve tissue than all other groups. There were no differences in print length factor after 12 weeks or conduction veloc ity at sacrifice between any groups. Tolerance induction was not demon strated. During mAb administration, animals in higher dose groups expe rienced temporary systemic side effects. This study demonstrated that a short course of mAb therapy directed against ICAM-1/LFA-1 inhibits r ejection in rat peripheral nerve allografts by an unknown mechanism. T he use of immune modulation in nerve transplantation may eliminate the need for systemic immunosuppression.