Department of Neurology, University Hospital of Regensburg, Regensburg, Germany.
Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, Regensburg, Germany.
Front Immunol. 2020 Oct 8;11:563645. doi: 10.3389/fimmu.2020.563645. eCollection 2020.
Alemtuzumab (anti-CD52 mAb) leads to a long-lasting disease activity suppression in patients with relapsing forms of multiple sclerosis (MS). In this study, we examined the change of the immune cell repertoire and the cellular reactivity after treatment with alemtuzumab. We analyzed the number of IFN-γ-secreting cells in presence of several peptides which had been eluted from the central nervous system (CNS) of MS patients and are possible targets of autoreactive T cells in MS. The patients showed a stabilized disease activity measured in clinical parameters and lesion formation after the treatment. We detected a reduction of the number of IFN-γ-secreting cells in the presence of every tested self-antigen. The number of IFN-γ-secreting cells was also reduced in the presence of non-self-antigens. We also found a clear change in the immune cell repertoire. After an almost complete depletion of all lymphocytes, the cell specificities showed different reconstitution patterns, resulting in different cell fractions. The percentage of CD4+ T cells was clearly reduced after therapy, whereas the fractions of B and NK cells were elevated. When we evaluated the number of IFN-γ-secreting cells in relation to the number of present CD4+ T cells, we still found a significant reduction. We conclude that the reduction of IFN-γ-secreting cells by alemtuzumab is not only due to a reduction of the CD4+ T cell fraction within the peripheral blood mononuclear cell (PBMC) compartment but might also be caused by functional changes or a shift in the distribution of different subtypes in the CD4+ T cell pool.
阿仑单抗（抗 CD52mAb）可使复发性多发性硬化症（MS）患者的疾病活动长期受到抑制。在这项研究中，我们检查了在用阿仑单抗治疗后免疫细胞库和细胞反应性的变化。我们分析了在存在从 MS 患者中枢神经系统（CNS）洗脱的几种肽的情况下 IFN-γ 分泌细胞的数量，这些肽可能是 MS 中自身反应性 T 细胞的靶标。治疗后，患者的疾病活动度（通过临床参数和病变形成来衡量）得到稳定。我们在存在每种测试的自身抗原的情况下均检测到 IFN-γ 分泌细胞数量减少。在存在非自身抗原的情况下，IFN-γ 分泌细胞的数量也减少了。我们还发现免疫细胞库发生了明显变化。在几乎耗尽所有淋巴细胞后，细胞特异性显示出不同的重建模式，导致不同的细胞群。治疗后 CD4+T 细胞的百分比明显降低，而 B 和 NK 细胞的分数升高。当我们根据存在的 CD4+T 细胞数量评估 IFN-γ 分泌细胞的数量时，我们仍然发现有显著减少。我们得出结论，阿仑单抗引起的 IFN-γ 分泌细胞减少不仅归因于外周血单个核细胞（PBMC）区 CD4+T 细胞分数的减少，而且可能是由于功能变化或不同 CD4+T 细胞池的不同亚型分布的转移所致。
