Metastable Tolerance to Rhesus Monkey Renal Transplants Is Correlated with Allograft TGF-β1+CD4+ T Regulatory Cell Infiltrates
| Autor: | Terry D. Oberley, Majed M. Hamawy, Jose R. Torrealba, Qingyong Xu, William J. Burlingham, Jacqueline M. Schultz, S Kusaka, Gaby G. M. Doxiadis, Margreet Jonker, Ronald E. Bontrop, Masaaki Katayama, John H. Fechner, Ewa Jankowska-Gan, Jacqueline Wubben, Huaizhong Hu, Stuart J. Knechtle |
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| Rok vydání: | 2004 |
| Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection Pathology medicine.medical_specialty medicine.medical_treatment T cell Immunology Mice SCID Biology Peripheral blood mononuclear cell Transforming Growth Factor beta1 Mice Cell Movement T-Lymphocyte Subsets Transforming Growth Factor beta medicine Animals Transplantation Homologous Immunology and Allergy Hypersensitivity Delayed Graft Survival Immunosuppression Histology Kidney Transplantation Macaca mulatta Peripheral Transplantation medicine.anatomical_structure Leukocytes Mononuclear Transplantation Tolerance CD8 Transforming growth factor |
| Zdroj: | The Journal of Immunology. 172:5753-5764 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.172.9.5753 |
| Popis: | Approaches that prevent acute rejection of renal transplants in a rhesus monkey model were studied to determine a common mechanism of acceptance. After withdrawal of immunosuppression, all 14 monkeys retained normal allograft function for >6 mo. Of these, nine rejected their renal allograft during the study, and five maintained normal function throughout the study period. The appearance of TGF-β1+ interstitial mononuclear cells in the graft coincided with a nonrejection histology, whereas the absence/disappearance of these cells was observed with the onset of rejection. Analysis with a variety of TGF-β1-reactive Abs indicated that the tolerance-associated infiltrates expressed the large latent complex form of TGF-β1. Peripheral leukocytes from rejecting monkeys lacking TGF-β1+ allograft infiltrates responded strongly to donor Ags in delayed-type hypersensitivity trans-vivo assays. In contrast, allograft acceptors with TGF-β1+ infiltrates demonstrated a much weaker peripheral delayed-type hypersensitivity response to donor alloantigens (p < 0.01 vs rejectors), which could be restored by Abs that either neutralized active TGF-β1 or blocked its conversion from latent to active form. Anti-IL-10 Abs had no restorative effect. Accepted allografts had CD8+ and CD4+ interstitial T cell infiltrates, but only the CD4+ subset included cells costaining for TGF-β1. Our data support the hypothesis that the recruitment of CD4+ T regulatory cells to the allograft interstitium is a final common pathway for metastable renal transplant tolerance in a non-human primate model. |
| Databáze: | OpenAIRE |
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