Immunomodulatory effects of cytokine-induced expansion of cytotoxic lymphocytes in a mouse model of lupus-like disease.
Immunomodulatory effects of cytokine-induced expansion of cytotoxic lymphocytes in a mouse model of lupus-like disease.
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DOI：
10.1016/j.jcyt.2020.09.003
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发表时间：
2021-01
期刊：
影响因子：
4.5
通讯作者：
Waggoner SN
中科院分区：
文献类型：
--
作者：
Reighard SD;Krishnamurthy D;Cevik H;Ochayon DE;Ali A;Seelamneni H;Brunner HI;Waggoner SN
促进自然杀伤（NK）细胞扩增的某些疗法（即达克珠单抗）与多发性硬化症和相关小鼠模型背景下的疾病临床改善相关。临床益处无疑归因于NK细胞杀死活化的致病性T细胞的能力增强。目前尚不清楚这种平行的方法是否对系统性红斑狼疮（狼疮）也有效，狼疮是一种由自身反应性T和B细胞的异常反应驱动的多器官自身免疫性疾病。在本研究中，我们评估了IL-2和IL-15为基础的策略，扩大NK细胞的措施狼疮样疾病的小鼠模型的治疗效果。出乎意料的是，奎宁介导的细胞毒性淋巴细胞的扩增加重了狼疮样疾病的免疫措施。耗竭研究表明，这些基于精氨酸的方案的负面影响在很大程度上归因于CD 8 T细胞而不是NK细胞的扩增。这些结果引发了使用基于细胞因子的治疗方法治疗狼疮患者合并癌症的谨慎态度，并强调需要选择性扩增NK细胞的新方法，以进一步评估其在自身免疫性疾病中的临床价值。
Certain therapies (i.e. 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. In the present study we 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. Unexpectedly, cytokine-mediated expansion of cytotoxic lymphocytes aggravated immunological measures of lupus-like disease. Depletion studies reveal that the negative effects of these cytokine-based regimens can largely be attributed to expansion of CD8 T cells rather than NK cells. 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 in order to further assess their clinical value in autoimmune disease.
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影响因子：
--
作者：
Bailey CP;Budak-Alpdogan T;Sauter CT;Panis MM;Buyukgoz C;Jeng EK;Wong HC;Flomenberg N;Alpdogan O
通讯作者：
Alpdogan O
DOI：
10.1073/pnas.0601335103
发表时间：
2006-04-11
影响因子：
11.1
作者：
Bielekova, B;Catalfamo, M;Martin, R
通讯作者：
Martin, R
DOI：
10.4049/jimmunol.1100789
发表时间：
2011-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jiang W;Chai NR;Maric D;Bielekova B
通讯作者：
Bielekova B
DOI：
10.1084/jem.20151722
发表时间：
2016-05-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Domeier PP;Chodisetti SB;Soni C;Schell SL;Elias MJ;Wong EB;Cooper TK;Kitamura D;Rahman ZS
通讯作者：
Rahman ZS
DOI：
10.1016/j.berh.2017.09.013
发表时间：
2017-06
期刊：
Best practice & research. Clinical rheumatology
影响因子：
--
作者：
Choi MY;Flood K;Bernatsky S;Ramsey-Goldman R;Clarke AE
通讯作者：
Clarke AE