Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion
| Autor: | Elizabeth Strobert, Laura B. Higginbotham, Alfred Joseph Tector, Joseph M. Ladowski, Andrew B. Adams, Eric M. Walters, David V. Mathews, Alton B. Farris, Joe B. Jenkins, Gregory Martens, Cynthia P. Breeden, Christian P. Larsen, Allison Stephenson, Matthew Tector, Steven C. Kim |
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| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
Graft Rejection Swine Xenotransplantation medicine.medical_treatment 030230 surgery Lymphocyte Depletion Article Andrology 03 medical and health sciences 0302 clinical medicine Long term survival Biopsy Immune Tolerance medicine Animals Immunology and Allergy Pharmacology (medical) Transplantation Kidney biology medicine.diagnostic_test business.industry Graft Survival Immunosuppression biology.organism_classification Kidney Transplantation Macaca mulatta Rhesus macaque medicine.anatomical_structure biology.protein Heterografts Antibody business CD8 |
| Zdroj: | Am J Transplant |
| ISSN: | 1600-6135 |
| Popis: | The shortage of available organs remains the greatest barrier to expanding access to transplantation. Despite advances in genetic editing and immunosuppression, survival in experimental models of kidney xenotransplantation has generally been limited to 400 days vs 6 days). These studies suggested that CD4(+) T cells may have a more prominent role in xenograft rejection compared to CD8(+) T cells. While animals that received selective depletion of CD8(+) T cells showed signs of early cellular rejection (marked CD4(+) infiltrates), animals receiving selective CD4(+) depletion exhibited normal biopsies until late where signs of chronic antibody rejection were present. In-vitro studies suggested that rhesus CD4(+) T cells required the presence of SLA class II to mount an effective proliferative response. The combination of low pre-transplant anti-pig antibody and CD4 depletion resulted in consistent, long-term xenograft survival. |
| Databáze: | OpenAIRE |
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