Anti-CD40L monoclonal antibody treatment induces long-term, tissue-specific, immunologic hyporesponsiveness to peripheral nerve allografts.
The CD40/CD40L costimulatory pathway plays a crucial role in allograft rejection. The purpose of this study was to determine the effectiveness of anti-CD40L monoclonal antibody (mAb) treatment as a method to induce long-term, tissue-specific, immunologic hyporesponsiveness to peripheral nerve allografts. Sciatic nerve allografts were performed from BALB/c donor mice into C57BL/6 recipients. Anti-CD40L mAb (1 mg) was administered intraperitoneally to recipient mice on postoperative days 0, 1, and 2. After a 14-, 28-, or 60-day recovery period, the mice were rechallenged with either a BALB/c cardiac or peripheral nerve allograft. Rejection was assessed by measuring the production of interferon gamma (IFN-gamma), interleukin (IL)-2, -4, and -5, and alloantibodies immunoglobulin (Ig) M and IgG. IFN-gamma, IL-2, IL-4, IL-5, IgM, and IgG responses were much lower in the anti-CD40L mAb group compared with controls. Nerve allograft and nerve isograft rechallenge 60 days following the original nerve allotransplantation produced low cytokine responses, whereas cardiac allograft rechallenge produced high cytokine production, indicative of acute rejection. Short-term anti-CD40L treatment may cause long-term, tissue-specific, immunologic hyporesponsiveness. This may allow time for native axons to traverse the transplanted nerve allograft and replace the graft with autogenous peripheral nerve tissue.
Mungara
Anil K
AK
Section of Plastic and Reconstructive Surgery, University of Michigan, Ann Arbor, MI, USA.
Brown
David L
DL
Bishop
D Keith
DK
Wood
Sherri Y
SY
Cederna
Paul S
PS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D023201:CD40 Ligand / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D006084:Graft Rejection; D006085:Graft Survival; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012584:Sciatic Nerve / Q000637:transplantation*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D023201:CD40 Ligand