Volume 7 Issue 3
May  2016
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Article Navigation >  ORGAN TRANSPLANTATION  > 2016  >  7(3): 171-176
Zhao Gaoping, Yang Maozhu, Li Shurong, et al. Effect of B cell-derived TGF-β on regulating antibody-induced immune tolerance after transplantation[J]. ORGAN TRANSPLANTATION, 2016, 7(3): 171-176. doi: 10.3969/j.issn.1674-7445.2016.03.002
Citation: Zhao Gaoping, Yang Maozhu, Li Shurong, et al. Effect of B cell-derived TGF-β on regulating antibody-induced immune tolerance after transplantation[J]. ORGAN TRANSPLANTATION, 2016, 7(3): 171-176. doi: 10.3969/j.issn.1674-7445.2016.03.002
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Effect of B cell-derived TGF-β on regulating antibody-induced immune tolerance after transplantation

doi: 10.3969/j.issn.1674-7445.2016.03.002

  • Department of Gastrointestinal Surgery,Sichuan Academy of Medical Science, Sichuan Provincial People's Hospital,the Affiliated Hospital of University of Electronic Science and Technology ofChina, Chengdu 610072, China

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    Abstract
  •   Objective  To investigate the regulatory function of transforming growth factor(TGF)-β in transplantation immune tolerance induced by anti-CD45RB antibody or in combination with anti-Tim-1 antibody.  Methods  Mouse models with allogeneic cardiac and pancreatic islet transplantation were established. The animals with allogeneic cardiac transplantation were treated with anti-CD45RB antibody and (or) anti-TGF-β antibody and those with pancreatic islet transplantation were handled with anti-CD45RB antibody in combination with anti-Tim-1 antibody supplemented with/without anti-TGF-β antibody. The long-term survival of transplant graft was observed. B cells from recipients which tolerated by pancreas islet transplantation for long time, were isolated and subsequently infused into the mouse models with islet cell transplantation. The survival of pancreas islet transplant graft was observed after anti-TGF-β antibody therapy. After double-antibody treatment in vitro for 14 d, B cell from recipients were mingled with lipopolysaccharide (LPS) and cultured overnight. The percentage of CD19+LAP+ cell was quantitatively measured by flow cytometer analysis.  Results  Six among 9 mice with allogeneic cardiac transplantation survived for a long term after anti-CD45RB antibody therapy. All cardiac grafts developed transplant rejection if use of anti-TGF-β antibody was supplemented. In mouse models with islet cell transplantation, combined use of anti-CD45RB and anti-Tim-1 antibodies induced long-term immune tolerance in 90% of transplant grafts. No transplant graft survived for a long period after anti-TGF-β antibody was delivered. Following B cell infusion, 8 of 9 pancreas islet grafts induced no transplant rejection, whereas yielded transplant rejection immediately after supplementing anti-TGF-β antibody. B cells were stimulated and cultured in vitro. Flow cytometry analysis revealed the proportion of CD19+LAP+ cells in B cells was significantly elevated (P < 0.0001).  Conclusions  Immune tolerance induced by anti-CD45RB antibody or in combination with anti-Tim-1 antibody depends on TGF-β, probably regulated by regulatory B cells.

     

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