Key role for CD4 T cells during mixed antibody-mediated rejection of renal allografts.
Key role for CD4 T cells during mixed antibody-mediated rejection of renal allografts.
复制标题
DOI：
10.1111/ajt.12596
复制
发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Hadley GA
中科院分区：
文献类型：
--
作者：
Gaughan A;Wang J;Pelletier RP;Nadasdy T;Brodsky S;Roy S;Lodder M;Bobek D;Mofatt-Bruce S;Fairchild RL;Henry ML;Hadley GA
我们利用小鼠模型来阐明混合抗体介导的肾移植排斥反应（混合AMR）期间移植物功能丧失的免疫学机制，其中对移植物的体液和细胞反应同时发生。尽管在排斥反应时移植物中的大多数T细胞是CD8 T细胞，只有少量的CD4 T细胞，但CD4细胞的耗竭而不是CD8细胞的耗竭防止了混合AMR期间的急性移植物丢失。CD4耗竭消除了抗供体同种异体抗体，并赋予保护免受肾移植物的破坏。ELISPOT结果显示，CD4 T效应细胞通过直接和间接的同种异体识别途径对供体抗原产生应答。在转移研究中，致敏供体同种异体抗原的CD4 T效应细胞在促进急性移植物功能障碍方面非常有效，并表现出效应T细胞的属性。激光捕获显微切割和确证性免疫染色研究表明，浸润移植物的CD4 T细胞产生具有移植物破坏潜力的效应分子。生物发光成像证实，CD4 T效应交通的移植部位在免疫充分的主机。这些数据表明，宿主CD4 T细胞除了促进抗供体同种抗体反应外，还可通过直接介导移植物损伤来促进肾移植物的急性功能障碍。
We utilized mouse models to elucidate the immunologic mechanisms of functional graft loss during mixed antibody mediated rejection of renal allografts (mixed AMR), in which humoral and cellular responses to the graft occur concomitantly. Although the majority of T cells in the graft at the time of rejection were CD8 T cells with only a minor population of CD4 T cells, depletion of CD4 but not CD8 cells prevented acute graft loss during mixed AMR. CD4 depletion eliminated anti-donor alloantibodies and conferred protection from destruction of renal allografts. ELISPOT revealed that CD4 T effectors responded to donor alloantigens by both the direct and indirect pathways of allorecognition. In transfer studies, CD4 T effectors primed to donor alloantigens were highly effective at promoting acute graft dysfunction, and exhibited the attributes of effector T cells. Laser capture microdissection and confirmatory immunostaining studies revealed that CD4 T cells infiltrating the graft produced effector molecules with graft destructive potential. Bioluminescent imaging confirmed that CD4 T effectors traffic to the graft site in immune replete hosts. These data document that host CD4 T cells can promote acute dysfunction of renal allografts by directly mediating graft injury in addition to facilitating anti-donor alloantibody responses.
登录
查看更多内容
DOI：
10.1084/jem.172.6.1735
发表时间：
1990-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu Y;Janeway CA Jr
通讯作者：
Janeway CA Jr
影响因子：
6
作者：
Bickerstaff, Alice;Pelletier, Ronald;Naclasdy, Tibor
通讯作者：
Naclasdy, Tibor
影响因子：
8.8
作者：
Bickerstaffa, A.;Nozaki, T.;Fairchild, R. L.
通讯作者：
Fairchild, R. L.
影响因子：
4.4
作者：
Nakashima, S;Qian, ZP;Baldwin, WM
通讯作者：
Baldwin, WM
脱敏肾移植受者急性同种异体移植功能障碍的发病机制
影响因子：
2.1
作者：
Singh, N.;Sun, Q.;Pelletier, R. P.
通讯作者：
Pelletier, R. P.