Portal de Periódicos da CAPES

Immunological Unresponsiveness in Chimeric Miniature Swine following MHC-Mismatched Spleen Transplantation

2005; Wolters Kluwer; Volume: 80; Issue: 12 Linguagem: Inglês

10.1097/01.tp.0000184625.27076.c8

1534-6080

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

Organ and Tissue Transplantation Research

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 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.