Immunological unresponsiveness in chimeric miniature swine following MHC-mismatched spleen transplantation

Frank J.M.F. Dor, Yau Lin Tseng, Kenji Kuwaki, Bernd Gollackner, Mario L. Ramirez, Derek D. Prabharasuth, Robert A. Cina, Christoph Knosalla, Matthew G. Nuhn, Stuart L. Houser, Christene A. Huang, Dicken S.C. Ko, David K.C. Cooper

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background. In rodents, spleen allotransplantation (SpTx) induces tolerance. We investigated the induction of chimerism and donor-specific unresponsiveness following pig SpTx. Methods. Thirteen pigs underwent splenectomy (day 0); all received a blood transfusion. In 11/13 pigs, SpTx was performed across a MHC class I (n = 1) or full (n = 10) barrier; two control pigs received no SpTx. All pigs were monitored for chimerism, and anti-donor immune responses, including suppressor assays. Four pigs (two asplenic controls and two with SpTx) underwent delayed donor-matched kidney transplantation without immunosuppression. Results. Six of the 11 spleen grafts were lost from rejection (n = 5) or splenic vein thrombosis (n = 1), and five remained viable. All 11 SpTx recipients developed multilineage chimerism, but chimerism was rapidly lost if the graft failed. Two control pigs showed <6% blood chimerism for 4 and 11 days only. Pigs with functioning spleen grafts had multilineage chimerism in blood, thymus and bone marrow for at least 2-6 months, without graft-versus-host disease. These pigs developed in vitro donor-specific hyporesponsiveness and suppression. In 2 pigs tolerant to the spleen graft, donor MHC-matched kidney grafts survived for >4 and >7 months in the absence of exogenous immunosuppression; in two asplenic pigs, kidney grafts were rejected on days 4 and 15. Conclusions. Successful SpTx can result in hematopoietic cell engraftment and in vitro donor-specific unresponsiveness, enabling prolonged survival of subsequent donor-matched kidney grafts without immunosuppression.

Original languageEnglish
Pages (from-to)1791-1804
Number of pages14
JournalTransplantation
Volume80
Issue number12
DOIs
Publication statusPublished - 2005 Dec

All Science Journal Classification (ASJC) codes

  • Transplantation

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