The Induction of Tolerance of Renal Allografts by Adoptive Transfer in Miniature Swine

• Published in: American journal of transplantation Vol. 13; no. 5; pp. 1193 - 1202
• Main Authors: Okumi, M., Scalea, J. R., Gillon, B. C., Tasaki, M., Villani, V., Cormack, T., Hirakata, A., Shimizu, A., Sachs, D. H., Yamada, K.
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley 01.05.2013; Wiley Subscription Services, Inc
• Subjects: Adoptive transfer; Adoptive Transfer - methods; Animals; Biological and medical sciences; Flow Cytometry; Graft Rejection - immunology; Graft Rejection - prevention & control; Graft Survival; Immunosuppressive Agents - therapeutic use; kidney transplantation; Kidney Transplantation - immunology; Lymphocyte Culture Test, Mixed; Medical sciences; MGH miniature swine; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the urinary system; Swine; Swine, Miniature; tolerance; Transplantation Tolerance - immunology; Transplantation, Homologous; Induction; Tolerance; Homotransplantation; Kidney; Adoptive transfer; Vertebrata; Mammalia; Treatment; Urinary system; Swine; MGH miniature swine; Surgery; Animal; Graft; Artiodactyla; Triggering; Ungulata; Kidney transplantation
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/ajt.12194

Our previous in vitro data have demonstrated that regulatory mechanisms are involved in tolerance of class I‐mismatched renal allografts in miniature swine treated with 12 days of high dose Cyclsporin A. In this study, we attempted to induce tolerance of class I‐mismatched kidneys by adoptive transfer of cells and/or kidneys from long‐term tolerant animals. Fifteen SLAdd miniature swine received 1.5 Gy whole body irradiation and class I‐mismatched (SLAgg) kidneys from naïve pigs with or without cotransplanted kidneys and/or adoptively transferred cells from long‐term tolerant (LTT) SLAdd recipients of SLAgg grafts. In addition, three SLAdd miniature swine received class I mismatched kidney with adoptively transferred cells from LTT SLAdd recipients. Naïve kidneys transplanted without a LTT kidney were rejected within 9 days. All recipients of naive kidneys along with cells and kidney grafts from LTT animals showed markedly prolonged survival of the naive renal grafts (day 28, >150 and >150 days). These studies suggest that (1) tolerated kidneys have potent regulatory effects and (2) cells from LTT animals infused in conjunction with kidney grafts augment these regulatory effects. To our knowledge, these studies represent the first demonstration of successful adoptive transfer of tolerance in large animals. Utilizing MHC inbred miniature swine, the authors report that tolerance can be adoptively transferred across a class I mismatched (class II matched) barrier by transplanting tolerated kidneys as well as peripheral blood mononuclear cells into naïve animals.