Immunological unresponsiveness in chimeric miniature swine following MHC-mismatched spleen transplantation.
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.
Dor
Frank J M F
FJ
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Tseng
Yau-Lin
YL
Kuwaki
Kenji
K
Gollackner
Bernd
B
Ramirez
Mario L
ML
Prabharasuth
Derek D
DD
Cina
Robert A
RA
Knosalla
Christoph
C
Nuhn
Matthew G
MG
Houser
Stuart L
SL
Huang
Christene A
CA
Ko
Dicken S C
DS
Cooper
David K C
DK
D000818:Animals; D001803:Blood Transfusion; D003114:Colony-Forming Units Assay; D006084:Graft Rejection / Q000276:immunology; D006650:Histocompatibility Testing; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use; D007668:Kidney / Q000166:cytology; D016030:Kidney Transplantation / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008991:Monitoring, Physiologic; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000637:transplantation*; D013156:Splenectomy; D013552:Swine; D013556:Swine, Miniature; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology / Q000502:physiology
D007166:Immunosuppressive Agents