Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.
Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.
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DOI：
10.1371/journal.ppat.1009858
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发表时间：
2021-10
期刊：
影响因子：
6.7
通讯作者：
Li Z
中科院分区：
文献类型：
--
作者：
Zhou P;Chen J;He J;Zheng T;Yunis J;Makota V;Alexandre YO;Gong F;Zhang X;Xie W;Li Y;Shao M;Zhu Y;Sinclair JE;Miao M;Chen Y;Short KR;Mueller SN;Sun X;Yu D;Li Z
自身免疫性疾病通常用糖皮质激素和免疫抑制药物治疗，这可能会增加感染的风险，从而恶化疾病并导致死亡。低剂量IL-2 （ld - IL-2）治疗成为一种治疗多种自身免疫性疾病的新方法。为了研究其对感染的影响，我们回顾性研究了665例系统性红斑狼疮（SLE）患者，其中约三分之一接受了ld - il - 2治疗，其中ld - il - 2治疗有助于降低感染的发生率。与这项临床观察一致，IL-2治疗加速了感染甲型流感病毒或淋巴细胞性脉络丛脑膜炎病毒（LCMV）的小鼠的病毒清除。值得注意的是，尽管IL-2治疗增强了LCMV感染的抗病毒免疫，但却加剧了CD8+ T细胞介导的免疫病理。综上所述，ld - il - 2治疗降低了SLE患者的感染风险，增强了对病毒感染的控制，但应注意避免潜在的CD8+ T细胞介导的免疫病理。机会性感染导致自身免疫性疾病患者的疾病夸张，是导致死亡的主要原因。皮质类固醇和免疫抑制疗法通常会增加感染的风险。低剂量IL-2治疗作为一种治疗多种炎症和自身免疫性疾病的有前景的新疗法而出现，但这种治疗对感染的效果尚未得到系统评估。在这项回顾性研究中，发现低剂量IL-2治疗与系统性红斑狼疮（SLE）患者感染发生率降低有关。在甲型流感和淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染的小鼠模型中，IL-2治疗增强了CD8+ T细胞的效应功能，加速了病毒清除，但加重了CD8+ T细胞介导的急性LCMV感染的免疫病理。我们的研究结果表明，低剂量IL-2治疗可能特别有益于自身免疫性疾病患者，这些患者由于免疫功能受损而感染风险增加，例如CD8+ T细胞功能降低，但应谨慎避免潜在的CD8+ T细胞介导的免疫病理。
Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8+ T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology. Opportunistic infections cause disease exaggeration in patients with autoimmune diseases, representing a leading cause of mortality. Corticosteroids and immunosuppressive therapies often increase the risk of infections. Low-dose IL-2 therapy emerged as a promising new therapy to treat a wide range of inflammatory and autoimmune disorders, but the effect of this therapy to infections has not been systemically evaluated. In this retrospective study, Low-dose IL-2 therapy was found to be associated with the reduced incidence of infection in systemic lupus erythematosus (SLE) patients. In mouse models of influenza A and lymphocytic choriomeningitis virus (LCMV) infection, IL-2 treatment enhanced the effector function of CD8+ T cells and accelerated viral clearance but exacerbated CD8+ T cell-mediated immunopathology in acute LCMV infection. Our findings show that Low-dose IL-2 therapy might particularly benefit autoimmune disease patients with increased risk of infection due to compromised immunity, such as reduced CD8+ T cell function, but caution should be taken to avoid potential CD8+ T cell-mediated immunopathology.
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DOI：
10.1084/jem.20122462
发表时间：
2013-06-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gasteiger G;Hemmers S;Firth MA;Le Floc'h A;Huse M;Sun JC;Rudensky AY
通讯作者：
Rudensky AY
DOI：
10.4049/jimmunol.1000423
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fulton RB;Meyerholz DK;Varga SM
通讯作者：
Varga SM
影响因子：
15.9
作者：
Gong, Fang;Dai, Yaping;Zhou, Pengcheng
通讯作者：
Zhou, Pengcheng
影响因子：
100.3
作者：
Chen, Zeyu;John Wherry, E.
通讯作者：
John Wherry, E.
影响因子：
13.3
作者：
Feldman, Candace H.;Hiraki, Linda T.;Winkelmayer, Wolfgang C.;Marty, Francisco M.;Franklin, Jessica M.;Kim, Seoyoung C.;Costenbader, Karen H.
通讯作者：
Costenbader, Karen H.