Hao Guo1, Wei Wang, Na Zhao, Xianghui He, Liwei Zhu, Xueming Jiang. 1. Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China; Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin 300052, China. Electronic address: guohaoay@163.com.
Abstract
BACKGROUND: Regulatory T (Treg) cells play a pivotal role in the maintenance of transplantation tolerance. It is of great interest to induce allograft tolerance mediated by regulatory CD4(+)CD25(+) T cells. METHODS: Here we investigated the effect of hydrodynamic IL-35-expressing plasmid injection in combination with a methyltransferase inhibitor (decitabine) on immune function and transplantation tolerance in mice. RESULTS: We showed that IL-35 and decitabine stimulated the proliferation of CD4(+)CD25(+) Tregs and suppressed CD8(+) T cell proliferation in an allogenic mixed lymphocyte culture in vitro. IL-35 gene therapy and decitabine administration prolonged the survival of the transplanted heart in the heterotopic abdominal heart transplantation model in mice. CONCLUSIONS: The possible mechanism through which IL-35 and decitabine treatment increased the survival of graft tissues is to enhance the proliferation of CD4(+)CD25(+) Treg cells and suppress the generation and function of effector T cells. Thus, IL-35 gene therapy combined with decitabine provides a novel approach to induce transplantation tolerance.
BACKGROUND: Regulatory T (Treg) cells play a pivotal role in the maintenance of transplantation tolerance. It is of great interest to induce allograft tolerance mediated by regulatory CD4(+)CD25(+) T cells. METHODS: Here we investigated the effect of hydrodynamic IL-35-expressing plasmid injection in combination with a methyltransferase inhibitor (decitabine) on immune function and transplantation tolerance in mice. RESULTS: We showed that IL-35 and decitabine stimulated the proliferation of CD4(+)CD25(+) Tregs and suppressed CD8(+) T cell proliferation in an allogenic mixed lymphocyte culture in vitro. IL-35 gene therapy and decitabine administration prolonged the survival of the transplanted heart in the heterotopic abdominal heart transplantation model in mice. CONCLUSIONS: The possible mechanism through which IL-35 and decitabine treatment increased the survival of graft tissues is to enhance the proliferation of CD4(+)CD25(+) Treg cells and suppress the generation and function of effector T cells. Thus, IL-35 gene therapy combined with decitabine provides a novel approach to induce transplantation tolerance.
Authors: Yanli Zou; Xiao Hu; Lauren P Schewitz-Bowers; Madeleine Stimpson; Li Miao; Xiaofei Ge; Liu Yang; Yan Li; Paul W Bible; Xiaofeng Wen; Jing Jing Li; Yizhi Liu; Richard W J Lee; Lai Wei Journal: Front Immunol Date: 2019-08-16 Impact factor: 7.561
Authors: Sija Landman; Chiel van der Horst; Piet E J van Erp; Irma Joosten; Rob de Vries; Hans J P M Koenen Journal: J Transl Med Date: 2021-01-06 Impact factor: 5.531