Priming with donor spleen cells and activated B cells can induce prolonged survival of class I-disparate skin allografts in cyclophosphamide-treated mice.
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 I-disparate combination.
Harada
M
M
Department of Virology and Immunology, Kyushu University, Fukuoka, Japan.
Omoto
K
K
Kimura
G
G
Nomoto
K
K
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D016038:Skin Transplantation / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D003520:Cyclophosphamide