Resident memory T cells form during persistent antigen exposure leading to allograft rejection.
Resident memory T cells form during persistent antigen exposure leading to allograft rejection.
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DOI：
10.1126/sciimmunol.abc8122
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发表时间：
2021-03-19
影响因子：
24.8
通讯作者：
Lakkis FG
中科院分区：
文献类型：
--
作者：
Abou-Daya KI;Tieu R;Zhao D;Rammal R;Sacirbegovic F;Williams AL;Shlomchik WD;Oberbarnscheidt MH;Lakkis FG
组织常驻记忆T细胞（TRM）包含在以前的感染部位提供局部保护，防止再次感染。它们是否在同源抗原存在的器官移植中形成和起作用尚不清楚。这是移植中的一个关键问题，因为在同种异体移植物中可以长期检测到T细胞，但不知道它们是耗尽的还是功能性记忆T细胞。通过小鼠肾移植模型，我们发现抗原特异性和多克隆效应T细胞在移植物中分化为TRM并随后引起同种异体移植排斥反应。在异种共生和再移植实验中，通过表面表型、转录谱和不能再循环来确定TRM的身份。移植物TRM局部增殖，在再次刺激时产生IFNγ，并且它们在体内的消耗减轻了排斥反应。重要的是，绝大多数抗原特异性和多克隆TRM缺乏表型和转录衰竭标记。移植后早期和晚期对移植物T细胞的单细胞分析发现了一个与向组织驻留状态过渡相关的转录程序，这可以作为发现治疗靶点的平台。因此，受体效应T细胞分化为维持局部排斥反应的功能性移植物TRM。靶向这些TRM可以改善肾移植的预后。受体效应T细胞分化为功能性组织常驻记忆T细胞，引起肾移植后的移植排斥反应。
Tissue resident memory T cells (TRM) contained at sites of previous infection provide local protection against re-infection. Whether they form and function in organ transplants where cognate antigen persists is unclear. This is a key question in transplantation as T cells are detected long-term in allografts, but it is not known whether they are exhausted or are functional memory T cells. Using a mouse model of kidney transplantation, we showed that antigen-specific and polyclonal effector T cells differentiated in the graft into TRM and subsequently caused allograft rejection. TRM identity was established by surface phenotype, transcriptional profile, and inability to recirculate in parabiosis and re-transplantation experiments. Graft TRM proliferated locally, produced IFNγ upon re-stimulation, and their in vivo depletion attenuated rejection. Importantly, the vast majority of antigen-specific and polyclonal TRM lacked phenotypic and transcriptional exhaustion markers. Single cell analysis of graft T cells early and late after transplantation identified a transcriptional program associated with transition to the tissue resident state that could serve as a platform for the discovery of therapeutic targets. Thus, recipient effector T cells differentiate into functional graft TRM that maintain rejection locally. Targeting these TRM could improve renal transplant outcomes. Recipient effector T cells differentiate into functional tissue resident memory T cells, causing graft rejection after kidney transplantation.
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影响因子：
14.9
作者：
Babicki S;Arndt D;Marcu A;Liang Y;Grant JR;Maciejewski A;Wishart DS
通讯作者：
Wishart DS
DOI：
10.1084/jem.20191711
发表时间：
2020-10-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kok L;Dijkgraaf FE;Urbanus J;Bresser K;Vredevoogd DW;Cardoso RF;Perié L;Beltman JB;Schumacher TN
通讯作者：
Schumacher TN
影响因子：
15.9
作者：
Hughes, Andrew D.;Zhao, Daqiang;Lakkis, Fadi G.
通讯作者：
Lakkis, Fadi G.
影响因子：
8.8
作者：
Camirand, G.;Li, Q.;Lakkis, F. G.
通讯作者：
Lakkis, F. G.
影响因子：
6.2
作者：
IBRAHIM, S;DAWSON, DV;SANFILIPPO, F
通讯作者：
SANFILIPPO, F