Normally occurring NKG2D+CD4+ T cells are immunosuppressive and inversely correlated with disease activity in juvenile-onset lupus.
Normally occurring NKG2D+CD4+ T cells are immunosuppressive and inversely correlated with disease activity in juvenile-onset lupus.
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DOI：
10.1084/jem.20081648
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发表时间：
2009-04-13
期刊：
影响因子：
--
通讯作者：
Groh V
中科院分区：
文献类型：
--
作者：
Dai Z;Turtle CJ;Booth GC;Riddell SR;Gooley TA;Stevens AM;Spies T;Groh V
NKG 2D受体在与恶性肿瘤和某些自身免疫性疾病相关的配体接合时刺激自然杀伤细胞和T细胞应答。然而，持续NKG 2D配体表达的条件可导致免疫抑制。在癌症患者中，NKG 2D的MHC I类相关链A（云母）配体的肿瘤表达和脱落驱动NKG 2D + CD 4 + T细胞增殖性扩增，产生白细胞介素-10（IL-10）和转化生长因子-β以及Fas配体，在体外抑制旁观者T细胞增殖。在这里，我们发现，在幼年型系统性红斑狼疮（SLE）中，功能等同的NKG 2D + CD 4 + T细胞的频率增加与疾病活动性呈负相关，这表明这些T细胞可能具有调节作用。NKG 2D + CD 4 + T细胞对应于正常存在的小CD 4 T细胞亚群，其具有自身反应性，引发产生IL-10，与类风湿性关节炎和克罗恩病中发生的具有苦参碱诱导的NKG 2D表达的促炎性和细胞溶解性CD 4 T细胞明显不同。由于经典调节性T细胞功能在SLE中通常受损，因此免疫抑制性NKG 2D + CD 4 + T细胞在该疾病中功能未受损可能具有临床意义。
The NKG2D receptor stimulates natural killer cell and T cell responses upon engagement of ligands associated with malignancies and certain autoimmune diseases. However, conditions of persistent NKG2D ligand expression can lead to immunosuppression. In cancer patients, tumor expression and shedding of the MHC class I–related chain A (MICA) ligand of NKG2D drives proliferative expansions of NKG2D+CD4+ T cells that produce interleukin-10 (IL-10) and transforming growth factor-β, as well as Fas ligand, which inhibits bystander T cell proliferation in vitro. Here, we show that increased frequencies of functionally equivalent NKG2D+CD4+ T cells are inversely correlated with disease activity in juvenile-onset systemic lupus erythematosus (SLE), suggesting that these T cells may have regulatory effects. The NKG2D+CD4+ T cells correspond to a normally occurring small CD4 T cell subset that is autoreactive, primed to produce IL-10, and clearly distinct from proinflammatory and cytolytic CD4 T cells with cytokine-induced NKG2D expression that occur in rheumatoid arthritis and Crohn's disease. As classical regulatory T cell functions are typically impaired in SLE, it may be clinically significant that the immunosuppressive NKG2D+CD4+ T cells appear functionally uncompromised in this disease.
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影响因子：
15.3
作者：
Gerosa, F;Paganin, C;Peritt, D;Paiola, F;Scupoli, MT;AsteAmezaga, M;Frank, I;Trinchieri, G
通讯作者：
Trinchieri, G
影响因子：
29.4
作者：
Allez, Matthieu;Tieng, Vannary;Toubert, Antoine
通讯作者：
Toubert, Antoine
影响因子：
56.9
作者：
Bauer, S;Groh, V;Spies, T
通讯作者：
Spies, T
影响因子：
9.1
作者：
Chun, Hye-Young;Chung, Jae-Wook;Suh, Chang-Hee
通讯作者：
Suh, Chang-Hee
影响因子：
2.2
作者：
Horton, Helen;Thomas, Evan P.;De Rosa, Stephen C.
通讯作者：
De Rosa, Stephen C.