SHP-1 in T cells limits the production of CD8 effector cells without impacting the formation of long-lived central memory cells.
SHP-1 in T cells limits the production of CD8 effector cells without impacting the formation of long-lived central memory cells.
复制标题
DOI：
10.4049/jimmunol.1001362
复制
发表时间：
2010-09-15
期刊：
影响因子：
--
通讯作者：
Greenberg PD
中科院分区：
文献类型：
--
作者：
Fowler CC;Pao LI;Blattman JN;Greenberg PD
在针对病毒和恶性肿瘤的反应期间，幼稚CD 8 T淋巴细胞扩增以形成短寿命效应细胞（SLEC）和含有具有长寿潜力并参与记忆反应（MPEC）的细胞的群体。反应期间抗原、共刺激和细胞因子信号的强度影响形成的CD 8群体的大小和类型。体外研究表明，酪氨酸磷酸酶SHP-1调节来自T细胞上受体（包括TCR）的信号转导，帮助设定活化阈值，因此可以在体内形成成熟CD 8 T细胞的反应。对来自SHP-1全面缺陷的飞蛾小鼠的CD 8 T细胞的分析证明是有问题的，这是由于非T细胞中SHP-1缺陷对CD 8 T细胞的细胞外在影响。因此，开发了成熟单阳性T细胞中SHP-1的条件性敲除，以分析完全和部分SHP-1缺陷对CD 8 T细胞对急性病毒感染的应答的细胞内在后果。结果表明，SHP-1对应答细胞的亚群具有不同的影响，通过减少产生的SLEC的数量而不影响导致长期记忆形成的MPEC池的大小来限制初级和次级应答的幅度和质量。
During responses against viruses and malignancies, naïve CD8 T lymphocytes expand to form both short-lived effector cells (SLECs) and a population containing cells with the potential to be long-lived and participate in memory responses (MPECs). The strength of antigenic, costimulatory, and cytokine signals during responses impacts the magnitude and type of CD8 populations formed. In vitro studies have revealed that the tyrosine phosphatase SHP-1 regulates signal transduction from receptors on T cells including the TCR, helping set the activation threshold, and therefore may shape responses of mature CD8 T cells in vivo. Analysis of CD8 T cells from motheaten mice, which are globally deficient in SHP-1, proved problematic due to cell-extrinsic effects of SHP-1 deficiency in non-T cells on CD8 T cells. Therefore, a conditional knockout of SHP-1 in mature single positive T cells was developed to analyze cell-intrinsic consequences of complete and partial SHP-1 deficiency on CD8 T cell responses to acute viral infection. The results demonstrated that SHP-1 has disparate effects on subpopulations of responding cells, limiting the magnitude and quality of primary and secondary responses by reducing the number of SLECs generated without affecting the size of the MPEC pool that leads to formation of long-term memory.
登录
查看更多内容
DOI：
10.1084/jem.20001021
发表时间：
2002-03-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Blattman JN;Antia R;Sourdive DJ;Wang X;Kaech SM;Murali-Krishna K;Altman JD;Ahmed R
通讯作者：
Ahmed R
影响因子：
4.4
作者：
Chemnitz, JM;Parry, RV;Riley, JL
通讯作者：
Riley, JL
影响因子：
8.7
作者：
Lorenz U
通讯作者：
Lorenz U
DOI：
10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolumam GA;Thomas S;Thompson LJ;Sprent J;Murali-Krishna K
通讯作者：
Murali-Krishna K
影响因子：
4.8
作者：
Cuevas, B;Lu, YL;Mills, GB
通讯作者：
Mills, GB