Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma.
Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma.
复制标题
CD4 T细胞中的PTEN损失增强了其辅助功能，但不会导致自身免疫性或淋巴瘤。
DOI：
10.4049/jimmunol.1102116
复制
发表时间：
2012-06-15
期刊：
影响因子：
--
通讯作者：
Okkenhaug K
中科院分区：
文献类型：
--
作者：
Soond DR;Garçon F;Patton DT;Rolf J;Turner M;Scudamore C;Garden OA;Okkenhaug K
Pten是人类癌症中最常见的肿瘤抑制剂之一，拮抗PI3K通路的信号传导。胸腺细胞特异性Pten缺失的小鼠迅速发展为外周淋巴瘤和自身免疫，这可能是由于胸腺细胞的阴性选择失败或胸腺后T细胞的失调。我们使用敲入Tnfrsf4（OX40）基因座的Cre从CD4辅助T细胞诱导Pten的条件性缺失以产生OX40CrePtenf小鼠。Pten缺陷的辅助性T细胞增殖更多，并产生更高浓度的细胞因子。OX40CrePtenf小鼠的淋巴结中淋巴细胞数量普遍增加，但脾脏中没有。当转移到野生型小鼠中时，Pten缺陷型辅助T细胞增强了抗李斯特菌反应，并在野生型T细胞没有影响的条件下清除肿瘤。此外，炎症反应被夸大，并解决晚于OX40CrePtenf小鼠比野生型小鼠。然而，与胸腺细胞特异性Pten缺失模型相反，即使在较老的OX40CrePtenf小鼠中也未观察到淋巴瘤和自身免疫。因此，Pten的丧失增强辅助性T细胞功能而没有明显的有害作用。
Pten, one of the most common tumor suppressors in human cancers, antagonizes signaling by the PI3K pathway. Mice with thymocyte-specific deletion of Pten rapidly developed peripheral lymphomas and autoimmunity, which may have been due to failed negative selection of thymocytes or from dysregulation of post-thymic T cells. We induced conditional deletion of Pten from CD4 helper T cells using a Cre knocked into the Tnfrsf4 (OX40) locus to generate OX40CrePtenf mice. Pten-deficient helper T cells proliferated more and produced higher concentrations of cytokines. The OX40CrePtenf mice had a general increase in the number of lymphocytes in the lymph nodes, but not in the spleen. When transferred into wild-type mice, Pten-deficient helper T cells enhanced anti-Listeria responses and the clearance of tumors under conditions in which wild-type T cells had no effect. Moreover, inflammatory responses were exaggerated and resolved later than in OX40CrePtenf mice than in wild type mice. However, in contrast to models of thymocyte-specific Pten deletion, lymphomas and autoimmunity were not observed, even in older OX40CrePtenf mice. Hence, loss of Pten enhances helper T cell function without obvious deleterious effects.
登录
查看更多内容
蛋白激酶B控制着指导细胞毒性T细胞命运但对于T细胞代谢的转录程序。
影响因子：
32.4
作者：
Macintyre AN;Finlay D;Preston G;Sinclair LV;Waugh CM;Tamas P;Feijoo C;Okkenhaug K;Cantrell DA
通讯作者：
Cantrell DA
影响因子：
82.9
作者：
Barber, DF;Bartolomé, A;Carrera, AC
通讯作者：
Carrera, AC
影响因子：
20.3
作者：
Newrzela, Sebastian;Cornils, Kerstin;von Laer, Dorothee
通讯作者：
von Laer, Dorothee
影响因子：
4.4
作者：
Barber, DF;Bartolomé, A;Carrera, AC
通讯作者：
Carrera, AC
影响因子：
32.4
作者：
Nombela-Arrieta, C;Lacalle, RA;Stein, JV
通讯作者：
Stein, JV