Palanichamy Arumugam, Jahn Sarah, Nickles Dorothee, Derstine Mia, Abounasr Aya, Hauser Stephen L, Baranzini Sergio E, Leppert David, von Büdingen H-Christian
University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.
Department of Neurology, University Hospital, Basel, Switzerland.
J Immunol. 2014 Jul 15;193(2):580-586. doi: 10.4049/jimmunol.1400118. Epub 2014 Jun 13.
In multiple sclerosis (MS), B cell-depleting therapy using monoclonal anti-CD20 Abs, including rituximab (RTX) and ocrelizumab, effectively reduces disease activity. Based on indirect evidence, it is generally believed that elimination of the Ag-presenting capabilities and Ag nonspecific immune functions of B cells underlie the therapeutic efficacy. However, a small subset of T lymphocytes (T cells) was shown to also express CD20, but controversy prevails surrounding the true existence of this T cell subpopulation. Using single-cell imaging flow cytometry and expression profiling of sorted lymphocyte subsets, we unequivocally demonstrate the existence of CD3(+)CD20(dim) T cells. We show that in MS patients, increased levels of CD3(+)CD20(dim) T cells are effectively depleted by RTX. The pathological relevance of this T cell subset in MS remains to be determined. However, given their potential proinflammatory functionality, depletion of CD20-expressing T cells may also contribute to the therapeutic effect of RTX and other mAbs targeting CD20.
在多发性硬化症（MS）中，使用包括利妥昔单抗（RTX）和奥瑞珠单抗在内的单克隆抗CD20抗体进行B细胞清除疗法可有效降低疾病活动度。基于间接证据，人们普遍认为消除B细胞的抗原呈递能力和抗原非特异性免疫功能是治疗效果的基础。然而，一小部分T淋巴细胞（T细胞）也被证明表达CD20，但关于这一T细胞亚群的真实存在仍存在争议。通过单细胞成像流式细胞术和分选淋巴细胞亚群的表达谱分析，我们明确证实了CD3(+)CD20(dim) T细胞的存在。我们发现，在MS患者中，RTX可有效清除CD3(+)CD20(dim) T细胞升高的水平。该T细胞亚群在MS中的病理相关性仍有待确定。然而，鉴于其潜在的促炎功能，表达CD20的T细胞的清除也可能有助于RTX和其他靶向CD20的单克隆抗体的治疗效果。
