Signaling Lymphocytic Activation Molecule Family Member 7 Engagement Restores Defective Effector CD8+ T Cell Function in Systemic Lupus Erythematosus.
Signaling Lymphocytic Activation Molecule Family Member 7 Engagement Restores Defective Effector CD8+ T Cell Function in Systemic Lupus Erythematosus.
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DOI：
10.1002/art.40038
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
Tsokos GC
中科院分区：
文献类型：
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作者：
Comte D;Karampetsou MP;Yoshida N;Kis-Toth K;Kyttaris VC;Tsokos GC
SLE患者效应CD8+ T细胞功能受损，并与抗感染能力受损相关。已显示SLAMF7接合增强NK细胞脱粒。因此，我们表征了SLAMF7在从SLE患者和健康受试者的外周血分离的CD8+ T细胞亚群上的表达和功能。通过流式细胞术监测分离自SLE患者和健康对照的细胞上的CD8+ T细胞亚群分布、SLAMF7表达和细胞溶解酶（穿孔素、GzmA、GzmB）表达。在存在或不存在抗SLAMF7抗体的情况下，通过流式细胞术评估响应于病毒抗原刺激的CD107 a表达和IFNγ产生。响应于SLAMF7接合的抗病毒细胞毒性活性使用基于流式细胞术的测定来确定。SLE患者外周血CD8+ T细胞亚群分布改变，效应细胞亚群减少。来自SLE患者的记忆CD8+ T细胞显示SLAMF7的量减少，SLAMF7是一种表征效应CD8+ T细胞的表面受体。SLAMF7的连接增加了SLE和健康对照中响应抗原攻击的CD8+ T细胞脱粒能力和IFNγ产生细胞的百分比。此外，SLAMF7接合促进靶细胞响应于病毒抗原刺激的细胞毒性裂解。通过特异性mAb激活SLAMF7可恢复有缺陷的SLE效应CD8+ T细胞对病毒抗原的应答功能，并代表SLE的潜在治疗选择。
Effector CD8+ T cell function is impaired in SLE and associated with compromised ability to fight infections. SLAMF7 engagement has been shown to enhance NK cell degranulation. Thus, we characterized the expression and function of SLAMF7 on CD8+ T cells subsets isolated from peripheral blood of SLE patients and healthy subjects. CD8+ T cell subset distribution, SLAMF7 expression and cytolytic enzyme expression (perforin, GzmA, GzmB) were monitored on cells isolated from SLE patients and healthy controls by flow cytometry. CD107a expression and IFNγ production in response to viral antigenic stimulation were assessed by flow cytometry in the presence or absence of an anti-SLAMF7 antibody. The antiviral cytotoxic activity in response to SLAMF7 engagement was determined using a flow cytometry-based assay. The distribution of CD8+ T cell subsets is altered in the peripheral blood of SLE patients with decreased effector cell subpopulation. Memory CD8+ T cells from SLE patients display decreased amounts of SLAMF7, a surface receptor that characterizes effector CD8+ T cells. Ligation of SLAMF7 increases CD8+ T cell degranulation capacity and the percentage of IFNγ-producing cell in response to antigen challenge in SLE and healthy controls. Moreover, SLAMF7 engagement promotes cytotoxic lysis of target cells in response to viral antigenic stimulation. Activation of SLAMF7 through a specific mAb restores defective SLE effector CD8+ T cells function in response to viral antigens and represents a potential therapeutic option in SLE.