Monoclonal antibodies against ICAM-1 and LFA-1 prolong nerve allograft survival.
In a rat nerve allograft model, specific immunosuppression was approached with monoclonal antibodies (MAbs) against cell-surface molecules. After engraftment, recipients were treated with antiintercellular adhesion molecule-1 (ICAM-1) and antilymphocyte function-associated antigen-1 (LFA-1) MAbs for 14 days. Functional recovery was evaluated biweekly. Electrophysiological and histological assessments were performed at 6 and 16 weeks. Immunologic responsiveness in the recipients was assessed with a cytotoxic T lymphocyte (CTL) assay at 16 weeks and skin grafts at 18 weeks. The untreated allograft group demonstrated complete disruption of fascicular architecture with poor nerve regeneration. The MAb-treated allografts maintained well-organized nerve architecture with a dense population of well-myelinated fibers. These animals showed functional and electrophysiological recovery. Suppression of CTL activity was nerve donor specific and the survival time of nerve donor skin grafts was prolonged, suggesting induction of alloantigen-specific tolerance. MAbs therapy directed against ICAM-1/LFA-1 presents a new approach for the management of the peripheral nerve allograft response.
Nakao
Y
Y
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri.
MacKinnon
S E
SE
Hertl
M C
MC
Miyasaka
M
M
Hunter
D A
DA
Mohanakumar
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D004594:Electrophysiology; D006085:Graft Survival / Q000187:drug effects; D007165:Immunosuppression Therapy / Q000379:methods; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D009417:Nerve Tissue / Q000503:physiopathology / Q000637:transplantation*; D051381:Rats; D011915:Rats, Inbred BUF; D011917:Rats, Inbred Lew; D016038:Skin Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000473:pathology; D013979:Tibial Nerve / Q000473:pathology; D016378:Tissue Transplantation; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1