ANTI-MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II TREATMENT PREVENTS GRAFT REJECTION IN THE HAMSTER-TO-RAT CARDIAC XENOGRAFT
| Autor: | Nina Elizabeth Saxton, Barbara T. Janczynski, Karen Zinkewich-Peotti, Heather Margaret Ladyman, Roland Foulkes, Richard S. Smith, Rhona V. Hallaway, Andrew M. Nesbitt |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Graft Rejection
Male Combination therapy medicine.medical_treatment Transplantation Heterologous Hamster Cell Separation Pharmacology Antibodies Cricetinae Cyclosporin a Leukocytes medicine Animals Cytotoxic T cell B cell Transplantation Mesocricetus biology business.industry Graft Survival Antibody-Dependent Cell Cytotoxicity Histocompatibility Antigens Class II Immunotherapy Flow Cytometry Immunohistochemistry Rats medicine.anatomical_structure Immunology Cyclosporine biology.protein Heart Transplantation Antibody business Immunosuppressive Agents |
| Zdroj: | Transplantation. 67:1599-1606 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-199906270-00015 |
| Popis: | Background Several groups have achieved graft acceptance in the concordant hamster to rat model by using a combination of anti-proliferative drugs and conventional immunosuppressive therapy. However, such aggressive treatment often leads to the recipient dying with a functional xenograft, as a result of opportunistic infections. This study aimed to investigate the effects of a short course of therapy with an anti-MHC class II monoclonal antibody treatment (chimeric OX6 [cOX6]) in combination with cyclosporin A (CyA) in a concordant hamster-to-rat xenograft model. Methods Rats receiving hamster cardiac xenografts were given CyA or cOX6 alone or in combination and were monitored daily to assess the effect of treatment on graft survival. Additional studies monitored the effect of treatment on the production of cytolytic anti-hamster antibodies by the recipient and the deposition of immunoglobulin (Ig)M and complement factors within the xenograft. Results Treatment with CyA only had no effect on graft survival, whereas treatment with cOX6 increased graft survival time by 2 days. The median graft survival time for cOX6+CyA was 76 days. cOX6 treatment of rats having undergone transplants inhibited the rise in cytotoxic anti-hamster antibodies in peripheral blood until day 5, whereas combination therapy completely inhibited anti-hamster antibody formation. Fluorescence-activated cell sorter analysis showed treatment with cOX6 significantly reduced circulating B cell numbers until day 5. Anti-MHC class II treatment also markedly reduced the deposition of both IgM and C3. Anti-MHC class II treatment with CyA gives long term survival in concordant xenografts without severe side effects. Conclusions The mechanism of action of this combination is complex and could be caused by an initial inhibition of B cell function by the anti-MHC class II treatment and the subsequent inhibition of T cell dependent pathways by CyA. |
| Databáze: | OpenAIRE |
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