Session Time: 3:15pm-4:45pm
Presentation Time: 3:27pm-3:39pm
*Purpose: We have achieved greater than 6-month survivals in baboons that received vascularized thymus plus kidney xenotransplants (VT+K XTx). We assessed the thymic function and recipient immune responses >4 months post-transplant.
*Methods: Six baboon recipients that survived >4 months after VT+K XTx were studied. All animals underwent thymectomy and bilateral nephrectomy prior to XTx. Two received anti-CD154 mAb-based (129 and 193 days survivals) and the other four received anti-CD40 mAb-based immunosuppression (126, 154, 174 and 187 survivals). Three of the animals received grafts from GalTKO pig donors, without other transgenes, and three received grafts from hCD47+GalTKO pigs Tg for additional human complement +/- coagulation regulatory proteins. In vitro T cell responses as well as anti-donor antibodies were assessed using recipient PBMCs and kidney grafts. Graft cell infiltrates were examined with anti-CD3 and anti-FoxP3 Abs. Newly developed baboon T cells in peripheral blood were determined by anti-human CD3/CD4/CD31/CD45RA mAb.
*Results: All baboon recipients had stable renal function for the first 4 months. Some exhibited eventual increased serum creatinine (Cre) due to organ growth. No grafts showed signs of acute or chronic rejection histologically. All animals showed pig-specific hyporesponsiveness at all time points tested, including the day of euthanasia. Only one baboon, which was euthanized at POD187 due to SVC syndrome associated with MMF toxicity, developed anti-donor IgG after POD60 (PODs 90, 120 and 187), with no rise in Cre (0.6-0.9mg/dL), suggesting accommodation. The remaining five did not develop anti-pig Abs. One kidney displayed cell infiltrates around vessels without tubulitis or endothelialitis (biopsy at POD140) that were FoxP3+, consistent with Treg-rich organized lymphoid structures (TOLs). Three baboons (174, 187 and 193 days survivors) showed peripheral naïve recipient T cells, which gradually increased after POD60 post-VT+K XTx, suggesting recipient thymopoiesis in the donor pig thymus.
*Conclusions: Life-supporting porcine VT+K XTx in thymectomized baboon recipients led to new host T cell development and specific hyporesponsiveness to pig antigens, accompanied by development of FoxP3+ TOLs in the donor kidneys, without evidence of acute rejection.
To cite this abstract in AMA style:Okumura Y, Takeuchi K, Ariyoshi Y, Pomposelli T, Boyd L, Alper D, Miyake K, Okubo K, Arn S, Ayares D, Lorber M, Sykes M, Sachs D, Yamada K. Life-Supporting Pig Thymus Plus Kidney Transplantation Leads to Generation of New Baboon T-Cells and Swine-Specific Hyporesponsiveness [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/life-supporting-pig-thymus-plus-kidney-transplantation-leads-to-generation-of-new-baboon-t-cells-and-swine-specific-hyporesponsiveness/. Accessed August 3, 2021.
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