ITM2A is induced during thymocyte selection and T cell activation and causes downregulation of CD8 when overexpressed in CD4(+)CD8(+) double positive thymocytes.
ITM2A is induced during thymocyte selection and T cell activation and causes downregulation of CD8 when overexpressed in CD4(+)CD8(+) double positive thymocytes.
复制标题
DOI：
10.1084/jem.190.2.217
复制
发表时间：
1999-07-19
期刊：
影响因子：
--
通讯作者：
Bevan MJ
中科院分区：
文献类型：
--
作者：
Kirchner J;Bevan MJ
为了确定新的基因，参与积极选择的胸腺细胞，我们进行了聚合酶链反应（PCR）为基础的消减杂交之间的选择和非选择胸腺。在H-2b小鼠中，重组激活基因（RAG）无效背景下的OT-1 T细胞受体（TCR）转基因胸腺细胞被有效选择为CD 8谱系（RAG-2−/−OT-1，选择性胸腺），但在抗原加工相关转运蛋白（TAP）无效背景下（RAG-2−/−TAP-1−/−OT-1，非选择性胸腺）未被选择。我们在这里报告我们的一个基因，ITM 2A，其表达显着较高的T细胞在选择胸腺的研究。胸腺细胞亚群中ITM 2A的表达模式与阳性选择过程中的上调相关。此外，ITM 2A在胸腺中的表达高于脾或淋巴结中的表达，但在活化后可在外周T细胞中上调。ITM 2A的表达也在体内RAG-2−/−胸腺细胞中在CD 3交联后被诱导。我们表明，ITM 2A是一种II型膜糖蛋白，存在作为两个物种与表观Mr为45和43 kD，似乎主要定位于大的细胞质囊泡和高尔基体，但也表达在细胞表面上。在EL 4细胞表面上的表达随着佛波醇肉豆蔻酸酯乙酸酯（PMA）和离子霉素的激活而增加。最后，小鼠中在lck近端启动子控制下的ITM 2A的过表达导致CD 4 + CD 8+双阳性（DP）胸腺细胞中的CD 8的部分下调，以及CD 4 + CD 810胸腺细胞数量的相应增加。这种新的活化标记在胸腺细胞发育的可能作用进行了讨论。
To identify novel genes that are involved in positive selection of thymocytes, we performed polymerase chain reaction (PCR)-based subtractive hybridization between selecting and nonselecting thymi. OT-1 T cell receptor (TCR) transgenic thymocytes on a recombination activating gene (RAG) null background are efficiently selected into the CD8 lineage in H-2b mice (RAG-2−/−OT-1, selecting thymi), but are not selected on a transporter associated with antigen processing (TAP) null background (RAG-2−/−TAP-1−/−OT-1, nonselecting thymi). We report here our studies of one gene, ITM2A, whose expression is dramatically higher in T cells in the selecting thymus. The expression pattern of ITM2A in thymocyte subsets correlates with upregulation during positive selection. In addition, ITM2A expression is higher in the thymus than in either the spleen or lymph nodes, but can be upregulated in peripheral T cells upon activation. ITM2A expression was also induced in RAG-2−/− thymocytes in vivo upon CD3 cross-linking. We demonstrate that ITM2A is a type II membrane glycoprotein that exists as two species with apparent Mr of 45 and 43 kD and appears to localize primarily to large cytoplasmic vesicles and the Golgi apparatus, but is also expressed on the cell surface. Expression on the surface of EL4 cells increases with activation by phorbol myristate acetate (PMA) and ionomycin. Finally, overexpression of ITM2A under control of the lck proximal promoter in mice results in partial downregulation of CD8 in CD4+CD8+ double positive (DP) thymocytes, and a corresponding increase in the number of CD4+CD8lo thymocytes. Possible roles for this novel activation marker in thymocyte development are discussed.
登录
查看更多内容
DOI：
10.1084/jem.164.6.1988
发表时间：
1986-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hara T;Jung LK;Bjorndahl JM;Fu SM
通讯作者：
Fu SM
影响因子：
32.4
作者：
LINETTE, GP;GRUSBY, MJ;KORSMEYER, SJ
通讯作者：
KORSMEYER, SJ
影响因子：
32.4
作者：
He, YW;Deftos, ML;Bevan, MJ
通讯作者：
Bevan, MJ
影响因子：
5.4
作者：
BRANDLE, D;MULLER, S;PIRCHER, H
通讯作者：
PIRCHER, H
影响因子：
4.8
作者：
Deleersnijder, W;Hong, GZ;Merregaert, J
通讯作者：
Merregaert, J