Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice

CORC > 厦门大学 > 生命科学－已发表论文

	Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice
	Liang, Hua ; Liao, Chongxian ; Qi, Zhongquan ; Sha, Chuang ; Xie, Baiyi ; Chen, Jibing ; Xia, Junjie ; Wang, Yongzhi ; Yao, Qing ; Zhao, Yongxiang ; Liang H(梁华) ; Liao CX(廖崇先) ; Qi ZQ(齐忠权) ; Chen JB(陈继冰)
刊名	http://dx.doi.org/10.1016/j.trim.2009.09.003
	2010-02
关键词	GENERATION TRANSPLANTATION INDUCTION EFFECTOR CYCLOSPORINE SUBSETS
英文摘要	Key Project of Program of Science and Technology of Fujian Province of China [MKJ 2008-59]; Donor-reactive memory T (Tm) cells undermine transplanted organs more readily than naive T cells. Rapamycin (RAPA) and tacrolimus (FK-506) are current mainstay immunosuppressants used for preventing acute allograft rejection. Although their efficacy in suppressing naive T cell is established, their suppressing effect on memory T cells is undefined. This study was conducted to investigate the inhibiting capability of RAPA or FK-506 against transferred alloreactive CD4(+) Tm, cells in a mouse cardiac transplant model. We found that these drugs alone prolonged the median survival time (MST) of allograft from 5 days to 9 days in recipient mice with CD4(+) Tm infusion (P < 0.01), which however was not significantly longer than that (8 days) in untreated recipient mice without CD4(+) Tm infusion (naive control). Mean histologic rank of rejection activity in section of cardiac allograft on day 5 postgrafting was Grade 4 in the Tm control recipients versus Grade 3A in both of the immunosuppressant treatment recipients with CD4(+) Tm infusion. RAPA or FK-506 alone failed to completely suppress proliferation and differentiation of the alloreactive CD4(+) Tm, which was confirmed by in vitro mixed lymphocyte reaction (MLR) and by flow cytometry (FCM) of the splenocytes for detecting CD44(high)CD62L(-) effector/memory as well as CD69(+)/CD25(+) activation phenotype cells from the respective recipients. Furthermore, the agent alone didn't completely inhibit the activation of CD4(+) Tm, for serum level of IFN-gamma and its gene expression at the cardiac allograft from the immunosuppressant-treated recipients were as still high as the untreated naive control. Thus, RAPA or FK-506 alone couldn't completely suppress the proliferation and activation of the alloantigen-primed CD4(+) Tm cells responding to the alloantigen, indicating that alloreactive CD4(+) Tm was insensitive to these immunosuppressants. The characteristics of alloreactive CD4(+) Tm to resist immunosuppressants and its potency to initiate quick and vigorous rejection despite treatment with the immunosuppressant make it to be a critical barrier to prolongation of allograft survival and induction of transplant tolerance. (C) 2009 Elsevier B.V. All rights reserved.
语种	英语
出版者	TRANSPL IMMUNOL
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/90493]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Liang, Hua,Liao, Chongxian,Qi, Zhongquan,et al. Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice[J]. http://dx.doi.org/10.1016/j.trim.2009.09.003,2010.
APA	Liang, Hua.,Liao, Chongxian.,Qi, Zhongquan.,Sha, Chuang.,Xie, Baiyi.,...&陈继冰.(2010).Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice.http://dx.doi.org/10.1016/j.trim.2009.09.003.
MLA	Liang, Hua,et al."Rapamycin or tacrolimus alone fails to resist cardiac allograft accelerated rejection mediated by alloreactive CD4(+) memory T cells in mice".http://dx.doi.org/10.1016/j.trim.2009.09.003 (2010).