Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b.
Anergic CD4+ T cells form mature immunological synapses with enhanced accumulation of c-Cbl and Cbl-b.
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无能 CD4+ T 细胞形成成熟的免疫突触，并增强 c-Cbl 和 Cbl-b 的积累。
DOI：
10.4049/jimmunol.0902285
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发表时间：
2010-04-01
期刊：
影响因子：
--
通讯作者：
Wetzel SA
中科院分区：
文献类型：
--
作者：
Doherty M;Osborne DG;Browning DL;Parker DC;Wetzel SA
在共刺激信号的背景下，CD 4 + T细胞对MHC：肽复合物的识别导致分子在T-APC界面处的大规模重新分布以形成免疫突触。免疫突触是持续TCR信号传导和递送效应子功能子集的位置。在没有共刺激的情况下活化的T细胞被赋予无反应性，并且当在最佳共刺激存在下呈递抗原时是低反应性的。以前的几项研究已经研究了由无反应性T细胞形成的免疫突触的各个方面，但目前尚不清楚无反应性免疫突触的形成或组成是否存在差异。在这项研究中，我们通过孵育共刺激缺陷的转染成纤维细胞APC来使原代小鼠CD 4 + T细胞失活。使用TCR，MHC：肽，和ICAM-1染色的组合，我们发现，无反应性T细胞与特征的cSMAC和pSMAC域，是无法区分的控制突触的成熟的免疫突触。在无变应性突触处总磷酸酪氨酸有小幅增加沿着磷酸化ERK 1/2积累显著减少。最引人注目的是，c-Cbl和Cbl-b在无反应性突触中有特异性积聚。Cbl-b，以前被证明是必不可少的无反应性诱导，被发现在pSMAC和cSMAC的无反应性突触。这种Cbl-b（和c-Cbl）在无反应性突触处的积累可能在无反应性维持和/或诱导中起重要作用。
CD4+ T cell recognition of MHC:peptide complexes in the context of a costimulatory signal results in the large-scale redistribution of molecules at the T-APC interface to form the immunological synapse. The immunological synapse is the location of sustained TCR signaling and delivery of a subset of effector functions. T cells activated in the absence of costimulation are rendered anergic and are hyporesponsive when presented with antigen in the presence of optimal costimulation. Several previous studies have looked at aspects of immunological synapses formed by anergic T cells, but it remains unclear whether there are differences in the formation or composition of anergic immunological synapses. In this study we anergized primary murine CD4+ T cells by incubation of costimulation-deficient, transfected fibroblast APC. Using a combination of TCR, MHC:peptide, and ICAM-1 staining, we found that anergic T cells make mature immunological synapses with characteristic cSMAC and pSMAC domains that were indistinguishable from control synapses. There were small increases in total phosphotyrosine at the anergic synapse along with significant decreases in phosphorylated ERK 1/2 accumulation. Most striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses. Cbl-b, previously shown to be essential in anergy induction, was found in both the pSMAC and the cSMAC of the anergic synapse. This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an important role in anergy maintenance and/or induction.
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影响因子：
5.3
作者：
Balagopalan, Lakshmi;Barr, Valarie A.;Samelson, Lawrence E.
通讯作者：
Samelson, Lawrence E.
影响因子：
32.4
作者：
Cemerski, Saso;Das, Jayajit;Shaw, Andrey S.
通讯作者：
Shaw, Andrey S.
DOI：
10.1073/pnas.84.15.5409
发表时间：
1987-08-01
影响因子：
11.1
作者：
JENKINS, MK;PARDOLL, DM;SCHWARTZ, RH
通讯作者：
SCHWARTZ, RH
影响因子：
4.8
作者：
Denny, MF;Kaufman, HC;Straus, DB
通讯作者：
Straus, DB
影响因子：
30.5
作者：
Heissmeyer, V;Macián, F;Rao, A
通讯作者：
Rao, A