α/β-T CELL RECEPTOR-DIRECTED THERAPY IN RAT CARDIAC ALLOGRAFT RECIPIENTS
| Autor: | Wayne W. Hancock, Roland Kurrle, K Deusch, Frank Jakobs, Claus-Dieter Heidecke, Niko Zantl, Thomas Sewczik, Sören Westerholt, Jerzy W. Kupiec-Weglinski |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Graft Rejection
Male medicine.drug_class Receptors Antigen T-Cell alpha-beta medicine.medical_treatment Alpha (ethology) Pharmacology Monoclonal antibody Rats Inbred BN Animals Transplantation Homologous Medicine Beta (finance) Sensitization Heart transplantation Transplantation business.industry Myocardium Graft Survival Antibodies Monoclonal Immunohistochemistry Antibodies Anti-Idiotypic Rats medicine.anatomical_structure Rats Inbred Lew Immunology Heart Transplantation Skin grafting CD5 business |
| Zdroj: | Transplantation. 59:78-84 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/00007890-199501150-00014 |
| Popis: | An mAb directed to the alpha/beta-heterodimer of the rat T cell receptor was used to prevent rejection of cardiac allografts in sensitized (accelerated rejection) recipients. Over a wide dose range, alpha/beta-TCR-directed therapy abrogated accelerated rejection at 24-36 hr and extended cardiac allograft survival in a dose-dependent fashion, both when given after heart transplantation as well as during or before the sensitizing skin transplants (8.9 +/- 1.0 days, 12.7 +/- 0.6 days, or 8.7 +/- 1.5 days, respectively). Pretreatment with R73 completely abrogated host sensitization induced by skin grafting. As a result, post-heart transplant cyclosporine course (15 mg/kg for 7 day) has led to long-term graft acceptance (> 90 days vs. 15.2 +/- 1.6 days with postoperative CsA therapy alone). Administration of R73 mAb produced incomplete depletion (CD5+ cells) and partial modulation (alpha/beta-TCR/CD5 double-positive cells) in the peripheral blood. It suppressed in situ protein expression of many cytokines to background levels, in particular that of IL-2 and IFN-gamma, both when given after as well as before cardiac transplantation. However, only pretransplant mAb application was associated with augmented in situ elaboration of IL-4. alpha/beta-TCR-directed therapy induced strong host anti-idiotypic and, to a lesser degree, anti-isotypic antibody responses. Taken together, these results provide the rationale for a novel immunosuppressive strategy involving induction of hyporesponsiveness by alpha/beta-TCR-directed therapy before the alloantigenic exposure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|