细胞因子诱导的细胞毒性淋巴细胞扩增对狼疮样疾病小鼠模型的免疫调节作用。
Immunomodulatory effects of cytokine-induced expansion of cytotoxic lymphocytes in a mouse model of lupus-like disease.
机构信息
Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA; Immunology Graduate Training Program, Cincinnati, Ohio, USA.
Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
出版信息
Cytotherapy. 2021 Jan;23(1):37-45. doi: 10.1016/j.jcyt.2020.09.003. Epub 2020 Oct 20.
BACKGROUND AIMS
Certain therapies (e.g., daclizumab) that promote expansion of natural killer (NK) cells are associated with clinical amelioration of disease in the context of multiple sclerosis and associated mouse models. The clinical benefits are putatively attributable to an enhanced capacity of NK cells to kill activated pathogenic T cells. Whether a parallel approach will also be effective in systemic lupus erythematosus (lupus), a multi-organ autoimmune disease driven by aberrant responses of self-reactive T and B cells, is unclear.
METHODS
In the present study, the authors assess the therapeutic impact of IL-2- and IL-15-based strategies for expanding NK cells on measures of lupus-like disease in a mouse model.
RESULTS
Unexpectedly, cytokine-mediated expansion of cytotoxic lymphocytes aggravated immunological measures of lupus-like disease. Depletion studies revealed that the negative effects of these cytokine-based regimens can largely be attributed to expansion of CD8 T cells rather than NK cells.
CONCLUSIONS
These results provoke caution in the use of cytokine-based therapeutics to treat co-morbid cancers in patients with lupus and highlight the need for new methods to selectively expand NK cells to further assess their clinical value in autoimmune disease.
背景目的
某些促进自然杀伤 (NK) 细胞扩增的疗法（例如达利珠单抗）与多发性硬化症及其相关的小鼠模型中疾病的临床改善相关。这些临床获益据称归因于 NK 细胞增强了杀死激活的致病性 T 细胞的能力。在系统性红斑狼疮（狼疮）中，一种由自身反应性 T 和 B 细胞的异常反应驱动的多器官自身免疫性疾病中，是否也会采用类似的方法尚不清楚。
方法
在本研究中，作者评估了基于白细胞介素 2 (IL-2) 和白细胞介素 15 (IL-15) 的策略扩展 NK 细胞对狼疮样疾病小鼠模型中狼疮样疾病的治疗效果。
结果
出乎意料的是，细胞因子介导的细胞毒性淋巴细胞扩增加剧了狼疮样疾病的免疫指标。耗竭研究表明，这些细胞因子方案的负面效应主要归因于 CD8 T 细胞而非 NK 细胞的扩增。
结论
这些结果在狼疮患者伴发癌症时使用细胞因子治疗方法时需要谨慎，并强调需要新的方法来选择性地扩增 NK 细胞，以进一步评估其在自身免疫性疾病中的临床价值。
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