Priming with donor spleen cells and activated B cells can induce prolonged survival of class I-disparate skin allografts in cyclophosphamide-treated mice
Harada, M.; Omoto, K.; Kimura, G.; Nomoto, K.
Transplantation 60(5): 517-519
1995
ISSN/ISBN: 0041-1337 PMID: 7676505 Document Number: 441999
We have previously reported a method for inducing tolerance using cyclophosphamide (CP) in a murine model, in which 200 mg/kg of CP is administered intraperitoneally 2 days after intravenous priming with donor spleen cells. The CP-induced tolerance method, however, cannot induce long-lasting skin allograft survival in an MHC class I-disparate combination. In this study, we tried to explain this phenomenon based on a costimulatory theory. That is, allo-class I-reactive host CD8+ helper T cells may receive insufficient costimulatory signals from donor spleen cells and, therefore, they are resistant to subsequently administered CP. We demonstrated that activated donor B cells, which can deliver sufficient costimulatory signals, induce a more efficient proliferation of allo-class I-reactive host CD8+ helper T cells than naive B cells in vitro. In addition, we also demonstrated that our idea can also be applied to the CP-induced skin allograft tolerance in an MHC class 1-disparate combination.