IL-6 promotes cardiac graft rejection mediated by CD4+ cells.
IL-6 promotes cardiac graft rejection mediated by CD4+ cells.
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DOI：
10.4049/jimmunol.1100766
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发表时间：
2011-12-01
期刊：
影响因子：
--
通讯作者：
Bishop DK
中科院分区：
文献类型：
--
作者：
Booth AJ;Grabauskiene S;Wood SC;Lu G;Burrell BE;Bishop DK
IL-6介导许多与移植排斥相关的免疫学效应;然而，其对这些过程的具体贡献尚未完全了解。为此，我们在与CD 8+或CD 4+细胞显性反应相关的急性心脏同种异体移植排斥反应中中和IL-6。在CD 8+细胞占主导地位的移植物排斥反应的背景下，IL-6中和延迟了急性排斥反应的发生，同时减少了移植物浸润，并逆转了受体中抗移植物Th 1/Th 2的启动优势。在CD 4+细胞介导的急性排斥反应中，IL-6中和作用显著延长了移植物存活，并与移植物浸润减少、Th 1应答改变和血清同种抗体降低相关。此外，在CD 4+细胞主导的排斥反应中，当抗IL-6给药延迟多达移植后6天时，IL-6中和是有效的。最后，IL-6缺乏的移植物受体受到保护，从CD 4+细胞的优势反应表明，IL-6生产的移植物受体，而不是移植物，是必要的这种类型的排斥反应。累积起来，这些观察结果将IL-6定义为心脏移植物排斥中移植物浸润的关键促进剂和T细胞谱系发育的塑造者。鉴于这些发现，应考虑使用靶向IL-6的治疗剂来预防心脏移植排斥反应。
IL-6 mediates numerous immunologic effects relevant to transplant rejection; however its specific contributions to these processes are not fully understood. To this end, we neutralized IL-6 in settings of acute cardiac allograft rejection associated with either CD8+ or CD4+ cell dominant responses. In a setting of CD8+ cell dominant graft rejection, IL-6 neutralization delayed the onset of acute rejection while decreasing graft infiltrate and inverting anti-graft Th1/Th2 priming dominance in recipients. IL-6 neutralization markedly prolonged graft survival in the setting of CD4+ cell mediated acute rejection and was associated with decreased graft infiltrate, altered Th1 responses, and reduced serum alloantibody. Further, in CD4+ cell dominated rejection, IL-6 neutralization was effective when anti-IL-6 administration was delayed by as many as six days post-transplant. Finally, IL-6 deficient graft recipients were protected from CD4+ cell dominant responses suggesting that IL-6 production by graft recipients, rather than grafts, is necessary for this type of rejection. Cumulatively, these observations define IL-6 as a critical promoter of graft infiltration and a shaper of T cell lineage development in cardiac graft rejection. In light of these findings, the utility of therapeutics targeting IL-6 should be considered for preventing cardiac allograft rejection.
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影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
DOI：
10.1111/j.1600-6143.2009.02826.x
发表时间：
2010-02
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Booth AJ;Csencsits-Smith K;Wood SC;Lu G;Lipson KE;Bishop DK
通讯作者：
Bishop DK
DOI：
10.1084/jem.20081571
发表时间：
2009-01-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dienz O;Eaton SM;Bond JP;Neveu W;Moquin D;Noubade R;Briso EM;Charland C;Leonard WJ;Ciliberto G;Teuscher C;Haynes L;Rincon M
通讯作者：
Rincon M
影响因子：
6.7
作者：
Ehrchen JM;Roebrock K;Foell D;Nippe N;von Stebut E;Weiss JM;Münck NA;Viemann D;Varga G;Müller-Tidow C;Schuberth HJ;Roth J;Sunderkötter C
通讯作者：
Sunderkötter C
DOI：
10.4049/jimmunol.182.1.379
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Burrell BE;Lu G;Li XC;Bishop DK
通讯作者：
Bishop DK