Activation‐induced accumulation of B and T lymphocyte attenuator at the immunological synapse in CD4+ T cells
Activation‐induced accumulation of B and T lymphocyte attenuator at the immunological synapse in CD4+ T cells
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DOI：
10.1189/jlb.0309138
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发表时间：
2010-03
影响因子：
5.5
通讯作者：
T. Owada;N. Watanabe;Mie Oki;Yoshihiro Oya;Y. Saito;T. Saito;I. Iwamoto;T. Murphy;K. Murphy;H. Nakajima
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文献类型：
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作者：
T. Owada;N. Watanabe;Mie Oki;Yoshihiro Oya;Y. Saito;T. Saito;I. Iwamoto;T. Murphy;K. Murphy;H. Nakajima
BTLA是最近克隆的在淋巴细胞上表达的辅助受体，通过募集SHP-1/SHP-2来负调节细胞活化。然而，调节BTLA的细胞内定位及其在T细胞中向细胞表面运输的机制仍然未知。为了确定调节BTLA在T细胞表面上表达的机制，我们使用共聚焦激光扫描显微镜检查了稳态下小鼠T细胞中BTLA的亚细胞定位以及激活后的亚细胞定位。我们发现BTLA主要定位于静息CD 4 + T细胞的高尔基体和分泌溶酶体中。我们还发现，细胞内的BTLA易位到细胞表面，并积累在免疫突触后TCR刺激。此外，我们发现BTLA与脂筏的结合需要BTLA-HVEM相互作用。这些结果表明，BTLA的表面表达及其在免疫突触处的积累受到TCR和HVEM刺激的严格调节，以在调节CD 4 + T细胞活化中递送有效的抑制信号。
BTLA, a recently cloned coreceptor expressed on lymphocytes, negatively regulates cell activation by recruiting SHP‐1/SHP‐2. However, the mechanisms that regulate the intracellular localization of BTLA and its trafficking to the cell surface in T cells are still unknown. To determine the mechanisms that regulate the expression of BTLA on the surface of T cells, we examined the subcellular localization of BTLA in mouse T cells in a steady state, as well as upon activation by using a confocal laser‐scanning microscopy. We found that BTLA was localized mainly in the Golgi apparatus and secretory lysosomes in resting CD4+ T cells. We also found that intracellular BTLA was translocated to the cell surface and accumulated at the immunological synapse upon TCR stimulation. Furthermore, we found that the BTLA‐HVEM interaction was required for the association of BTLA with lipid rafts. These results indicate that the surface expression of BTLA and its accumulation at the immunological synapse are tightly regulated by TCR and HVEM stimulation to deliver efficient inhibitory signals in the regulation of CD4+ T cell activation.