Augmentation of Transient Donor Cell Chimerism and Alloantigen‐Specific Regulation of Lung Transplants in Miniature Swine. Issue 5 (22nd February 2016)

• Record Type: Journal Article
• Authors: Avsar, M.; Jansson, K.; Sommer, W.; Kruse, B.; Thissen, S.; Dreckmann, K.; Knoefel, A.‐K.; Salman, J.; Hafer, C.; Hecker, J.; Buechler, G.; Karstens, J. H.; Jonigk, D.; Länger, F.; Kaever, V.; Falk, C. S.; Hewicker‐Trautwein, M.; Ungefroren, H.; Haverich, A.; Strüber, M.; Warnecke, G.
• Is Part Of: American journal of transplantation. Volume 16:Issue 5(2016:May)
• Page Start: 1371
• Page End: 1382
• Publication Date: 2016-02-22
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13629
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex–mismatched single lung transplantation was performed in 28 minipigs followed by a 28‐day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low‐dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4 + CD25 high+ T cell frequencies were detected in peripheral blood associated with decreased interferon‐γ production of leukocytes. Secondary third‐party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third‐party splenocytes or donor splenocyte protein extracts. While animals treated with third‐party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third‐party, splenocyte infusions may develop long‐term donor‐specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells. Abstract : Early leukocyte chimerism increases with donor spleen cell infusion following low‐dose recipient irradiation in an outbred miniature swine lung transplantation model, resulting in long‐term lung allograft survival but preserved immune competence versus delayed third‐party kidney allografts.