Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hanover, Germany.
Department for Rheumatology and Immunology, Hanover Medical School, Hanover, Germany.
Ann Rheum Dis. 2021 Dec;80(12):1537-1544. doi: 10.1136/annrheumdis-2021-220435. Epub 2021 Jul 5.
The monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.
CD8 T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.
Rituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8 T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8 T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8 T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.
Depending on the stimulus, B cells can modulate CD8 T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8 T cell responses.
单克隆抗 CD20 抗体利妥昔单抗常用于治疗淋巴瘤和自身免疫性疾病，并能有效清除循环中的 B 细胞。相应地，B 细胞耗竭的患者在感染或接种疫苗期间几乎不会产生新的抗体反应。因此，B 细胞耗竭患者的有效免疫反应在很大程度上依赖于保护性 T 细胞反应。
研究了利妥昔单抗治疗的类风湿关节炎（RA）患者和 B 细胞缺陷小鼠在接种/感染不同疫苗/病原体时 CD8 T 细胞的扩增情况。
与健康对照组相比，接种 Influvac 的利妥昔单抗治疗的 RA 患者流感特异性 CD8 T 细胞的扩增减少。此外，感染适应性小鼠流感或改良安卡拉痘苗病毒的 JHT 小鼠的病毒特异性 CD8 T 细胞扩增不如野生型小鼠活跃。值得注意的是，JHT 小鼠没有内在的 CD8 T 细胞扩增缺陷，因为接种痘苗病毒可在 JHT 和野生型小鼠中诱导类似的 T 细胞扩增。B 细胞的 I 型干扰素受体信号直接作用于 B 细胞，以诱导 B 细胞中几种趋化因子的表达，并通过增强 MHC-I 的表达来支持 T 细胞辅助。
根据刺激的不同，B 细胞可以调节 CD8 T 细胞的反应。因此，B 细胞耗竭会导致新抗体反应的缺乏，并影响包括细胞毒性 T 细胞在内的细胞反应的疗效。必须重新评估为 B 细胞耗竭患者选择合适的疫苗，以有效诱导保护性 CD8 T 细胞反应。
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