title: Arsenic trioxide inhibits accelerated allograft rejection mediated by alloreactive CD8(+) memory T cells and prolongs allograft survival time.
abstract: CD8(+) memory T (Tm) cells are a significant barrier to transplant tolerance induction in alloantigen-primed recipients, and are insensitive to existing clinical immunosuppressants. Here, we studied the inhibition of CD8(+) Tm cells by arsenic trioxide (As2O3) for the first time. Alloantigen-primed CD8(+) Tm cells were transferred to T cell immunodeficient nude mice. The mice were subjected to heart allotransplantation, and treated with As2O3. The transplant survival time was determined, and the inhibitory effects of As2O3 on CD8(+) Tm cell-mediated immune rejection were assessed through serological studies and inspection of the transplanted heart and lymphoid organs. We found that As2O3 treatment prolonged the mean survival time of the graft and reduced the number of CD8(+) Tm cells in the spleen and lymph nodes. The expression of the genes encoding interleukin (IL)-2, and IFN-γ was reduced, while expression of IL-10 and transforming growth factor-β was increased in the transplant. Our findings show that As2O3 treatment inhibits allograft rejection mediated by alloreactive CD8(+) Tm cells in the mouse heart transplantation model.
authors.affiliation: Organ Transplantation Institute, Xiamen University, Xiamen City, Fujian Province, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Nephrology Department of Zhongshan Hospital, Xiamen University, Xiamen City, Fujian Province, PR China.
authors.forename: Tianjun
authors.initials: T
authors.lastname: Guan
authors.affiliation: Organ Transplantation Institute, Xiamen University, Xiamen City, Fujian Province, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Gao
authors.affiliation: Organ Transplantation Institute, Xiamen University, Xiamen City, Fujian Province, PR China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Basic Medical Department of Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Yan
authors.affiliation: Organ Transplantation Institute, Xiamen University, Xiamen City, Fujian Province, PR China.
authors.forename: Maoshu
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Chinese Medicine Department of Medical College, Xiamen University, Fujian Province, PR China.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Lv
authors.affiliation: Organ Transplantation Institute, Xiamen University, Xiamen City, Fujian Province, PR China. Electronic address: xia@xmu.edu.cn.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xia
authors.affiliation: Organ Transplantation Institute, Xiamen University, Xiamen City, Fujian Province, PR China. Electronic address: oti@xmu.edu.cn.
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D064591:Allografts; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010087:Oxides / Q000494:pharmacology*
chemical_list: D001152:Arsenicals; D016207:Cytokines; D010087:Oxides; D000077237:Arsenic Trioxide
keywords: Arsenic trioxide; CD8(+) memory T cells; Heart transplantation; Nude mice