Frischer J M, Reindl M, Künz B, Berger T, Schmidt S, Milford E L, Knosp E, Lassmann H, Utku N
Division of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Austria Department of Neurosurgery, Medical University of Vienna, Austria
Clinical Department of Neurology, Innsbruck Medical University, Austria.
Mult Scler. 2014 Aug;20(9):1171-81. doi: 10.1177/1352458514521516. Epub 2014 Feb 13.
Interactions between TIRC7 (a novel seven-transmembrane receptor on activated lymphocytes) and its ligand HLA-DR might be involved in the inflammatory process in multiple sclerosis (MS).
Methods comprised immunohistochemistry and microscopy on archival MS autopsies, proliferation-, cytokine-, and surface-staining assays using peripheral blood lymphocytes (PBLs) from MS patients and an in vitro model.
TIRC7 was expressed in brain-infiltrating lymphocytes and strongly correlated with disease activity in MS. TIRC7 expression was reduced in T cells and induced in B cells in PBLs obtained from MS patients. After ex vivo activation, T cell expression of TIRC7 was restored in patients with active MS disease. The interaction of TIRC7(+) T lymphocytes with cells expressing HLA-DR on their surface led to T cell proliferation and activation whereas an anti-TIRC7 mAb preventing interactions with its ligand inhibited proliferation and Th1 and Th17 cytokine expression in T cells obtained from MS patients and in myelin basic protein-specific T cell clone.
Our findings suggest that TIRC7 is involved in inflammation in MS and anti-TIRC7 mAb can prevent immune activation via selective inhibition of Th1- and Th17-associated cytokine expression. This targeting approach may become a novel treatment option for MS.
TIRC7（一种活化淋巴细胞上的新型七跨膜受体）与其配体HLA - DR之间的相互作用可能参与了多发性硬化症（MS）的炎症过程。
方法包括对存档的MS尸检样本进行免疫组织化学和显微镜检查，使用MS患者外周血淋巴细胞（PBL）进行增殖、细胞因子和表面染色检测以及体外模型。
TIRC7在脑浸润淋巴细胞中表达，且与MS的疾病活动度密切相关。在MS患者的PBL中，TIRC7在T细胞中的表达降低，而在B细胞中诱导表达。体外激活后，活动性MS疾病患者T细胞中TIRC7的表达得以恢复。TIRC7(+) T淋巴细胞与表面表达HLA - DR的细胞相互作用导致T细胞增殖和活化，而一种阻止其与配体相互作用的抗TIRC7单克隆抗体抑制了MS患者T细胞以及髓鞘碱性蛋白特异性T细胞克隆的增殖和Th1及Th17细胞因子表达。
我们的研究结果表明，TIRC7参与了MS的炎症过程，抗TIRC7单克隆抗体可通过选择性抑制Th1和Th17相关细胞因子表达来预防免疫激活。这种靶向方法可能成为MS的一种新型治疗选择。
