Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1.
Regulatory T cells suppress the late phase of the immune response in lymph nodes through P-selectin glycoprotein ligand-1.
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DOI：
10.4049/jimmunol.1301235
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发表时间：
2013-12-01
期刊：
影响因子：
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通讯作者：
Constantin G
中科院分区：
文献类型：
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作者：
Angiari S;Rossi B;Piccio L;Zinselmeyer BH;Budui S;Zenaro E;Della Bianca V;Bach SD;Scarpini E;Bolomini-Vittori M;Piacentino G;Dusi S;Laudanna C;Cross AH;Miller MJ;Constantin G
调节性T细胞（Tcells）维持对自身抗原的耐受性并抑制自身免疫性疾病，尽管其潜在的分子机制尚不清楚。在这项研究中，我们表明，小鼠缺乏P-选择素糖蛋白配体-1（PSGL-1）开发一个更严重的形式的实验性自身免疫性脑脊髓炎比野生型动物，这表明PSGL-1有一个作用，在自身免疫的负调节。我们发现，缺乏PSGL-1的T细胞不能抑制实验性自身免疫性脑脊髓炎，也不能抑制体内淋巴结中的T细胞增殖。使用双光子激光扫描显微镜在淋巴结，我们发现，PSGL-1的表达在TCL 4免疫后的早期T细胞引发的抑制没有作用。相反，PSGL-1缺陷型TCL 4丧失了调节T细胞运动的能力，并且未能抑制T细胞-树突状细胞接触和T细胞聚集，而T细胞聚集是免疫应答后期持续T细胞活化所必需的。值得注意的是，髓鞘特异性效应T细胞上的PSGL-1表达在淋巴结中的T细胞运动中没有作用。我们的数据表明，PSGL-1代表了一个以前未知的，阶段特异性机制Treg介导的抑制免疫反应和自身免疫诱导的持久性。
Regulatory T cells (Tregs) maintain tolerance toward self-antigens and suppress autoimmune diseases, although the underlying molecular mechanisms are unclear. In this study, we show that mice deficient for P-selectin glycoprotein ligand-1 (PSGL-1) develop a more severe form of experimental autoimmune encephalomyelitis than wild type animals do, suggesting that PSGL-1 has a role in the negative regulation of autoimmunity. We found that Tregs lacking PSGL-1 were unable to suppress experimental autoimmune encephalomyelitis and failed to inhibit T cell proliferation in vivo in the lymph nodes. Using two-photon laser-scanning microscopy in the lymph node, we found that PSGL-1 expression on Tregs had no role in the suppression of early T cell priming after immunization with Ag. Instead, PSGL-1-deficient Tregs lost the ability to modulate T cell movement and failed to inhibit the T cell–dendritic cell contacts and T cell clustering essential for sustained T cell activation during the late phase of the immune response. Notably, PSGL-1 expression on myelin-specific effector T cells had no role in T cell locomotion in the lymph node. Our data show that PSGL-1 represents a previously unknown, phase-specific mechanism for Treg-mediated suppression of the persistence of immune responses and autoimmunity induction.