Schuh Elisabeth, Berer Kerstin, Mulazzani Matthias, Feil Katharina, Meinl Ingrid, Lahm Harald, Krane Markus, Lange Rüdiger, Pfannes Kristina, Subklewe Marion, Gürkov Robert, Bradl Monika, Hohlfeld Reinhard, Kümpfel Tania, Meinl Edgar, Krumbholz Markus
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig Maximilian University, 82152 Martinsried, Germany; Department of Neuroimmunology, Center for Brain Research, Medical University, 1090 Vienna, Austria;
Max-Planck Institute of Biochemistry, 82152 Martinsried, Germany;
J Immunol. 2016 Aug 15;197(4):1111-7. doi: 10.4049/jimmunol.1600089. Epub 2016 Jul 13.
Monoclonal Abs against CD20 reduce the number of relapses in multiple sclerosis (MS); commonly this effect is solely attributed to depletion of B cells. Recently, however, a subset of CD3(+)CD20(+) T cells has been described that is also targeted by the anti-CD20 mAb rituximab. Because the existence of cells coexpressing CD3 and CD20 is controversial and features of this subpopulation are poorly understood, we studied this issue in detail. In this study, we confirm that 3-5% of circulating human T cells display CD20 on their surface and transcribe both CD3 and CD20. We report that these CD3(+)CD20(+) T cells pervade thymus, bone marrow, and secondary lymphatic organs. They are found in the cerebrospinal fluid even in the absence of inflammation; in the cerebrospinal fluid of MS patients they occur at a frequency similar to B cells. Phenotypically, these T cells are enriched in CD8(+) and CD45RO(+) memory cells and in CCR7(-) cells. Functionally, they show a higher frequency of IL-4-, IL-17-, IFN-γ-, and TNF-α-producing cells compared with T cells lacking CD20. CD20-expressing T cells respond variably to immunomodulatory treatments given to MS patients: they are reduced by fingolimod, alemtuzumab, and dimethyl fumarate, whereas natalizumab disproportionally increases them in the blood. After depletion by rituximab, they show earlier and higher repopulation than CD20(+) B cells. Taken together, human CD3(+)CD20(+) T cells pervade lymphatic organs and the cerebrospinal fluid, have a strong ability to produce different cytokines, and respond to MS disease modifying drugs.
抗CD20单克隆抗体可减少多发性硬化症（MS）的复发次数；通常认为这种作用完全归因于B细胞的耗竭。然而，最近发现了一种CD3(+)CD20(+) T细胞亚群，抗CD20单克隆抗体利妥昔单抗也可靶向作用于该亚群。由于共表达CD3和CD20的细胞的存在存在争议，且对该亚群的特征了解甚少，我们对此进行了详细研究。在本研究中，我们证实3%至5%的循环人T细胞表面表达CD20，并转录CD3和CD20。我们报告称，这些CD3(+)CD20(+) T细胞遍布胸腺、骨髓和二级淋巴器官。即使在没有炎症的情况下，它们也存在于脑脊液中；在MS患者的脑脊液中，它们的出现频率与B细胞相似。从表型上看，这些T细胞富含CD8(+)和CD45RO(+)记忆细胞以及CCR7(-)细胞。在功能上，与缺乏CD20的T细胞相比，它们产生IL-4、IL-17、IFN-γ和TNF-α的细胞频率更高。表达CD20的T细胞对给予MS患者的免疫调节治疗反应各异：它们会被芬戈莫德、阿仑单抗和富马酸二甲酯减少，而那他珠单抗会使它们在血液中的数量不成比例地增加。在用利妥昔单抗清除后，它们比CD20(+) B细胞表现出更早且更高的再增殖。综上所述，人CD3(+)CD20(+) T细胞遍布淋巴器官和脑脊液，具有强大的产生不同细胞因子的能力，并对MS疾病修饰药物有反应。
