Allograft acceptance despite differential strain-specific induction of TGF-beta/IL-10-mediated immunoregulation.
We examined the immune approaches that C57BI/6 and BALB/c mice take when treated to accept cardiac allografts. C57BI/6 mice accept DBA/2 cardiac allografts when treated with gallium nitrate (GN) or anti-CD40L mAb (MR1). These allograft acceptor mice fail to mount donor-reactive delayed type hypersensitivity (DTH) responses, and develop a donor-induced immunoregulatory mechanism that inhibits DTH responses. In contrast, BALB/c mice accept C57BI/6 cardiac allografts when treated with MR1 but not with GN. These allograft acceptor mice display modest donor-reactive DTH responses, and do not develop donor-induced immune regulation of DTH responses. Real-time PCR analysis of rejecting graft tissues demonstrated no strain-related skewing in the production of cytokines mRNAs. In related studies, C57BI/6 recipients of cytokine and alloantigen educated syngeneic peritoneal exudate cells (PECs) failed to mount DTH responses to the alloantigens unless neutralizing antibodies to transforming growth factor-beta (TGF-p were present at the DTH site demonstrating regulation of cell-mediated alloimmune responses. In contrast, BALB/c recipients of cytokine-and alloantigen-educated PECs expressed strong DTH responses to alloantigens demonstrating a lack of regulated alloimmunity. In conclusion, C57BI/6 mice respond to immunosuppression by accepting cardiac allografts and generating TGF-beta-related regulation of donor-reactive T cell responses, unlike BALB/c mice that do not generate these regulatory responses yet still can accept cardiac allografts.
Bickerstaff
Alice A
AA
The Ohio State University College of Medicine, Department of Surgery, Columbus 43210, USA. bickerstaff-1@medctr.osu.edu
Wang
Jiao-Jing
JJ
Xia
Dongyuan
D
Orosz
Charles G
CG
D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D016027:Heart Transplantation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D016212:Transforming Growth Factor beta; D016753:Interleukin-10