title: Inhibiting accelerated rejection mediated by alloreactive CD4(+) memory T cells and prolonging allograft survival by 1α,25-dihydroxyvitamin D(3) in nude mice.
abstract: Donor-reactive memory T cells are major barriers to long-term survival of transplanted organs due to their capacity to accelerate rejection. In this study we investigated the ability of 1α,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] to inhibit accelerated rejection mediated by alloreactive CD4(+) memory T cells and to prolong cardiac allograft survival in an adoptive T cell memory/heart transplant model of nude mice. In vitro, the proliferation of CD4(+) memory T cells was significantly inhibited by 1,25(OH)(2)D(3) and was restored following addition of exogenous IL-2. Compared with the control group, the mean survival time of cardiac allografts in the 1,25(OH)(2)D(3) group was prolonged from 6.5±0.3 to 20.2±0.8 days in vivo. Five days after transplantation, the levels of IL-2 and IFN-γ were reduced in the grafts and the recipient sera by 1,25(OH)(2)D(3) treatment, while that of IL-10 increased. The proportions of CD4(+) memory T cells and CD4(+)Foxp3(+) T cells, both in recipient spleen and lymph nodes, were lowered by 1,25(OH)(2)D(3) treatment when compared with the control group. Our data suggests that 1,25(OH)(2)D(3) inhibits expansion of CD4(+) memory T cells, possibly by inducing clonal anergy and/or clonal deletion, resulting in prolongation of cardiac allograft survival in nude mice. These results may provide a rational basis for exploiting 1,25(OH)(2)D(3) as a novel immunosuppressant targeting CD4(+) memory T cells.
authors.affiliation: Basic Medical Department of Medical College, Xiamen University, Xiamen City, Fujian Province, PR China. zhuanyiyan@126.com
authors.forename: Guoliang
authors.initials: G
authors.lastname: Yan
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xi
authors.forename: Shuangyue
authors.initials: S
authors.lastname: Xu
authors.forename: Jibing
authors.initials: J
authors.lastname: Chen
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.forename: Helong
authors.initials: H
authors.lastname: Dai
authors.forename: Panpan
authors.initials: P
authors.lastname: Cheng
authors.forename: Haibin
authors.initials: H
authors.lastname: Xiao
authors.forename: Zhongchen
authors.initials: Z
authors.lastname: Liu
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007156:Immunologic Memory / Q000187:drug effects*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D014184:Transplantation, Homologous; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D007376:Interleukin-2; D014815:Vitamins; D007371:Interferon-gamma; D002117:Calcitriol