A more persistent tolerance to islet allografts through bone marrow transplantation in minimal nonmyeloablative conditioning therapy.
BACKGROUND
Islet transplantation is a therapeutic approach to prevent diabetes complications. However, the side effects of the required lifelong immunosuppressive regimens to prevent graft rejection restrict the impact of type 1 diabetes. One strategy to overcome these limitations is tolerance induction and graft acceptance through hematopoietic chimerism. In this study we investigated whether tolerance to major histocompatibility complex (MHC) and minor-disparate islet allografts could be induced by minimal nonmyeloablative conditioning and whether more persistent donor-specific islet allografts were accepted if the grafts were implanted with simultaneous bone marrow cells.


METHODS
The donor and recipient mice were BALB/c(H-2(b)) and C57BL/6(H-2(d)), respectively. In group 1 streptozotocin-induced diabetic C57BL/6(H-2(d)) mice received only 500 islets of BALB/c(H-2(b)). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy total body irradiation and cyclophosphamide were given islet cells of BALB/c(H-2(b)), but group 3 were simultaneously given 30 x 10(6) BALB/c(H-2(b)) mice BMCs and islet cells similar to group 2.


RESULTS
We obtained 5% to 6% allogeneic donor chimerism and 60% graft survival at 80 days after islet transplantation in group 3. We observed lymphocyte infiltration around the islet without destruction of endocrine cells and the presence of strong insulin/glucagon-stained cells in group 3.


CONCLUSIONS
This minimal nonmyeloablative conditioning therapy induced donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c-->C57BL/6) mice and long-term islet graft survival was obtained through cotransplantation of bone marrow cells.
Lee
B-W
BW
Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
Lee
J I
JI
Oh
S H
SH
Ahn
Y R
YR
Chae
H Y
HY
Lee
M S
MS
Lee
M K
MK
Kim
K W
KW
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D007108:Immune Tolerance; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D019172:Transplantation Conditioning