Altered functional and biochemical response by CD8+ T cells that remain after tolerance.
Altered functional and biochemical response by CD8+ T cells that remain after tolerance.
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耐受后残留的 CD8 T 细胞改变了功能和生化反应。
DOI：
10.1093/intimm/13.8.1085
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发表时间：
2001
影响因子：
4.4
通讯作者：
Sherman,LA
中科院分区：
文献类型：
--
作者：
Murtaza,A;Nugent,CT;Tailor,P;Asensio,VC;Biggs,JA;Campbell,IL;Sherman,LA
为了进一步确定外周表达抗原耐受性的分子基础，我们将血凝素（HA）特异性细胞毒性T淋巴细胞（CTL）克隆的功能能力差异与生化事件相关，这些克隆来自对HA不耐受的常规B10.D2小鼠（D2克隆6）或来自对HA耐受的InsHA小鼠（InsHA克隆12）。D2克隆6，而不是InsHA克隆12，在体内转移到辐照的InsHA宿主后触发糖尿病。该致糖尿病克隆在用HA脉冲的抗原呈递细胞刺激后显示TCR γ链和ZAP-70的完全和持续的磷酸化。相比之下，InsHA克隆12仅显示TCR γ的部分磷酸化，而没有ZAP-70的磷酸化。在用同源抗原刺激后，在两个克隆中Lck活化或募集至TCR复合物中没有缺陷。InsHA克隆12中近端信号传导的这种缺陷可以通过增加通过CD 3-TCR复合物的信号强度来克服，表明InsHA克隆12的信号传导机制是功能性的。这些数据表明，在耐受诱导后可以从InsHA小鼠中回收的HA应答性CD 8 +T细胞对作为部分激动剂/拮抗剂的HA应答。
To further define the molecular basis of tolerance to a peripherally expressed antigen we have correlated differences in functional capacity with biochemical events in hemagglutinin (HA)-specific cytotoxic T lymphocyte (CTL) clones derived either from a conventional B10.D2 mouse that is not tolerant to HA (D2 Clone 6) or from an InsHA mouse that is tolerant to HA (InsHA Clone 12). D2 Clone 6, but not InsHA Clone 12, triggers diabetes followingin vivotransfer into irradiated InsHA hosts. This diabetogenic clone shows complete and sustained phosphorylation of TCR ζζ chain and ZAP-70 following stimulation with HA-pulsed antigen-presenting cells. In contrast, InsHA Clone 12 showed only partial phosphorylation of TCR ζζ and no phosphorylation of ZAP-70. There was no defect in activation or recruitment of Lck to the TCR complex in both the clones following stimulation with the cognate antigen. This deficiency in the proximal signaling in the InsHA Clone 12 could be overcome by increasing the strength of signal through the CD3–TCR complex, indicating that the signaling machinery of InsHA Clone 12 was functional. These data demonstrate that the HA-responsive CD8+T cells that can be retrieved from InsHA mice after tolerance induction respond to HA as a partial agonist/antagonist.