Resistance to the induction of mixed chimerism in spontaneously diabetic NOD mice depends on the CD40/CD154 pathway and donor MHC disparity.
Blockade of CD40/CD154 pathway has proven effective in promoting the induction of allogeneic mixed chimerism. Using NOD mouse model of human type 1 diabetes, we investigated whether allogeneic mixed chimerism can be induced in prediabetic NOD mice and in spontaneously diabetic NOD mice under nonmyeloablative and irradiation-free conditioning therapy and anti-CD154 mAb as a short-term posttransplant treatment. We found that spontaneously diabetic NOD mice are more resistant to the induction of allogeneic mixed chimerism than prediabetic NOD mice under our nonmyeloablative and irradiation-free conditioning therapy. This alloresistance in spontaneously diabetic NOD mice is dependent on the CD40/CD154 pathway and donor MHC disparity.
Luo
Bin
B
Department of Surgery, MMC 195, University of Minnesota, 420 Delaware Street S.E., Minneapolis, MN 55455, USA. zhiguang@tc.umn.edu
Wu
Tao
T
Pan
Yisheng
Y
Sozen
Hakan
H
Hao
Jianqiang
J
Zhang
Yu
Y
Sutherland
David E R
DE
Hering
Bernhard J
BJ
Guo
Zhiguang
Z
D000818:Animals; D000911:Antibodies, Monoclonal; D016026:Bone Marrow Transplantation; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D002678:Chimera / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016688:Mice, Inbred NOD / Q000235:genetics*; D011236:Prediabetic State / Q000276:immunology; D023001:Transplantation Tolerance
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D023201:CD40 Ligand