CD6 modulates thymocyte selection and peripheral T cell homeostasis.
CD6 modulates thymocyte selection and peripheral T cell homeostasis.
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DOI：
10.1084/jem.20151785
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发表时间：
2016-07-25
期刊：
影响因子：
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通讯作者：
Lozano F
中科院分区：
文献类型：
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作者：
Orta-Mascaró M;Consuegra-Fernández M;Carreras E;Roncagalli R;Carreras-Sureda A;Alvarez P;Girard L;Simões I;Martínez-Florensa M;Aranda F;Merino R;Martínez VG;Vicente R;Merino J;Sarukhan A;Malissen M;Malissen B;Lozano F
Orta-Mascaró、Lozano 和合作者首次对 CD6 缺陷小鼠进行了分析，表明该分子调节 T 细胞受体信号传导以及胸腺细胞和外周 T 细胞亚群选择的阈值。 CD6 糖蛋白是一种淋巴细胞表面受体，可能参与 T 细胞的发育和激活。 CD6 通过与 CD166/ALCAM（激活的白细胞细胞粘附分子）相互作用促进 T 细胞和抗原呈递细胞之间的粘附，并与免疫突触中心的 T 细胞受体 (TCR) 物理结合。然而，其在胸腺细胞发育和外周 T 细胞免疫反应中的确切作用仍有待确定。在这里，我们分析了 CD6 缺乏的体内后果。 CD6−/− 胸腺显示 CD4+ 和 CD8+ 单阳性亚群减少，双阳性胸腺细胞在体外对 TCR 交联的 Ca2+ 动员增加。骨髓嵌合体实验揭示了 CD6−/− T 细胞在发育过程中的 T 细胞自主选择劣势。对 TCR 转基因小鼠（OT-I 和 Marilyn）的分析证实，在不存在 CD6 的情况下会发生异常 T 细胞选择事件。 CD6−/− 小鼠表现出在一定水平的 TCR 信号强度或共刺激下产生的经历过抗原的外周 T 细胞的频率增加，例如效应/记忆（CD4+TEM 和 CD8+TCM）和调节（T reg）T 细胞。 CD6−/− T reg 细胞的抑制活性减弱，CD6−/− 小鼠对胶原蛋白表现出加剧的自身免疫反应。总的来说，这些数据表明 CD6 调节胸腺细胞选择的阈值以及几种外周 T 细胞亚群（包括 T reg 细胞）的生成和/或功能。
Orta-Mascaró, Lozano, and collaborators provide the first analysis of CD6-deficient mice, showing that this molecule modulates T cell receptor signaling and the threshold for thymocyte and peripheral T cell subset selection. The CD6 glycoprotein is a lymphocyte surface receptor putatively involved in T cell development and activation. CD6 facilitates adhesion between T cells and antigen-presenting cells through its interaction with CD166/ALCAM (activated leukocyte cell adhesion molecule), and physically associates with the T cell receptor (TCR) at the center of the immunological synapse. However, its precise role during thymocyte development and peripheral T cell immune responses remains to be defined. Here, we analyze the in vivo consequences of CD6 deficiency. CD6−/− thymi showed a reduction in both CD4+ and CD8+ single-positive subsets, and double-positive thymocytes exhibited increased Ca2+ mobilization to TCR cross-linking in vitro. Bone marrow chimera experiments revealed a T cell–autonomous selective disadvantage of CD6−/− T cells during development. The analysis of TCR-transgenic mice (OT-I and Marilyn) confirmed that abnormal T cell selection events occur in the absence of CD6. CD6−/− mice displayed increased frequencies of antigen-experienced peripheral T cells generated under certain levels of TCR signal strength or co-stimulation, such as effector/memory (CD4+TEM and CD8+TCM) and regulatory (T reg) T cells. The suppressive activity of CD6−/− T reg cells was diminished, and CD6−/− mice presented an exacerbated autoimmune response to collagen. Collectively, these data indicate that CD6 modulates the threshold for thymocyte selection and the generation and/or function of several peripheral T cell subpopulations, including T reg cells.