Anti-CD40L Monoclonal Antibody Treatment Induces Long-Term, Tissue-Specific, Immunologic Hyporesponsiveness to Peripheral Nerve Allografts

Anil K. Mungara; David L. Brown; D. Keith Bishop; Sherri Y. Wood; Paul S. Cederna

doi:10.1055/s-2008-1076085

Journal of Reconstructive Microsurgery, Inhaltsverzeichnis

J Reconstr Microsurg 2008; 24(3): 189-195
DOI: 10.1055/s-2008-1076085

Anti-CD40L Monoclonal Antibody Treatment Induces Long-Term, Tissue-Specific, Immunologic Hyporesponsiveness to Peripheral Nerve Allografts

Anil K. Mungara¹ , David L. Brown¹ , D. Keith Bishop² , Sherri Y. Wood² , Paul S. Cederna¹ ^, ³

¹Section of Plastic and Reconstructive Surgery, University of Michigan, Ann Arbor, MI
²Section of General Surgery, Deparment of Surgery and Graduate Program in Immunology, University of Michigan, Ann Arbor, MI
³Institute of Gerontology, University of Michigan, Ann Arbor, MI

Abstract

ABSTRACT

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-γ), interleukin (IL)-2, -4, and -5, and alloantibodies immunoglobulin (Ig) M and IgG. IFN-γ, 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.

KEYWORDS

Nerve allograft - anti-CD40L mAb - MR1

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Referenzen

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Paul S CedernaM.D. F.A.C.S.

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