Long-term islet allograft function in the absence of chronic immunosuppression: a case report of a nonhuman primate previously made tolerant to a renal allograft from the same donor.
Development of mixed chimerism by donor bone marrow transplantation (DBMT) has led to long-term tolerance of solid organ allografts in nonhuman primates. As an initial attempt to extend this approach to cellular transplant, islet transplant from the same donor was attempted in the recipient previously made tolerant to a kidney allograft.


METHODS
After the conditioning with ATG, total body irradiation, thymic irradiation, and splenectomy, DBMT was performed followed by 4 weeks of cyclosporine. Kidney transplantation and native nephrectomies were subsequently performed on day 89. After 2.8 years of DBMT, diabetes was induced by streptozocin (STZ) and islets from bone marrow and kidney donor were transplanted without immunosuppression.


RESULTS
After DBMT, the recipient developed chimerism and no evidence of kidney rejection for more than 1000 days. STZ induced diabetes was reversed after the islet transplantation. Islet biopsies demonstrated insulin staining without rejection. Although the recipient became diabetic 300 days after islet transplantation, viable transplanted islets were found in the liver and under the kidney capsule without any evidence of rejection.


CONCLUSIONS
Tolerance with a nonmyeloablative conditioning can allow successful pancreatic islet transplantation without immunosuppression. Because no histological evidence of rejection was identified, recurrent diabetes is presumed to be inadequate islet mass.
Kawai
T
T
Department of Surgery, Harvard Medical School and the Transplantation Unit, Massachusetts General Hospital, White 510, 55 Fruit Street, Boston, MA 02114, USA.
Sogawa
H
H
Koulmanda
M
M
Smith
R N
RN
O'Neil
J J
JJ
Wee
S L
SL
Boskovic
S
S
Sykes
M
M
Colvin
R B
RB
Sachs
D H
DH
Auchincloss
H
H
Cosimi
A B
AB
C  Ko
D S
DS
D000017:ABO Blood-Group System / Q000276:immunology; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002096:C-Peptide / Q000097:blood; D002469:Cell Separation / Q000379:methods; D016572:Cyclosporine / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D006085:Graft Survival / Q000276:immunology*; D006650:Histocompatibility Testing; D007165:Immunosuppression Therapy / Q000379:methods*; D007328:Insulin / Q000032:analysis; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008252:Macaca fascicularis; D008285:Major Histocompatibility Complex; D008297:Male; D013156:Splenectomy; D014184:Transplantation, Homologous / Q000276:immunology; D014916:Whole-Body Irradiation
D000017:ABO Blood-Group System; D000961:Antilymphocyte Serum; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D016572:Cyclosporine