CD8αα+MHC Class II+ Cell with the Capacity To Terminate Autoimmune Inflammation Is a Novel Antigen-Presenting NK-like Cell in Rats.
CD8αα+MHC Class II+ Cell with the Capacity To Terminate Autoimmune Inflammation Is a Novel Antigen-Presenting NK-like Cell in Rats.
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DOI：
10.4049/jimmunol.1601207
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发表时间：
2016-12-01
期刊：
影响因子：
--
通讯作者：
Lou Y
中科院分区：
文献类型：
--
作者：
Wu J;Carlock C;Ross A;Shim J;Lou Y
抑制预先存在的自身免疫性炎症的免疫耐受机制的发现可能为我们提供治疗自身免疫性疾病的新策略。在对大鼠模型自身免疫性肾小球肾炎自发恢复的研究中，我们发现了具有专业 APC 能力的 CD8αα+MHC-II+ 细胞。该细胞主动侵入发炎的靶组织，并通过选择性杀死效应自身反应性 T 细胞进一步终止正在进行的自身免疫炎症。现在，我们证明该细胞使用 Ly49s+ NK 细胞的细胞毒性机制来杀死靶 T 细胞。因此，该CD8αα+MHC-II+细胞是具有双重功能的抗原呈递NK样(AP-NK)细胞。通过抗原呈递与靶 T 细胞偶联后，使用靶 T 细胞上的非经典 MHC-I RT1CE16 作为配体来启动杀伤，从而杀死该细胞上的刺激性受体 Ly49s6 和辅助受体 CD8αα。因此，RT1CE16 表达升高的激活效应 T 细胞非常容易被 CD8αα+ AP-NK 细胞杀死。来自该细胞的颗粒溶细胞性穿孔素/颗粒酶 C 随后介导细胞毒性。因此，抑制颗粒酶C可有效减弱杀灭作用。由于 CD8αα+ AP-NK 细胞可以识别并消除发炎靶组织中的效应自身反应性 T 细胞，因此它不仅代表了一种参与免疫耐受的新型免疫细胞，而且是开发针对现有自身免疫性疾病的细胞疗法的潜在候选者。
Discovery of immune tolerance mechanisms, which inhibit pre-existing autoimmune inflammation, may provide us with new strategies for treating autoimmune diseases. We have identified a CD8αα+MHC-II+ cell with professional APC capacity during our investigation on spontaneous recovery from autoimmune glomerulonephritis in a rat model. This cell actively invades inflamed target tissue and further terminates an on-going autoimmune inflammation by selective killing of effector autoreactive T cells. Now, we showed that this cell used a cytotoxic machinery of Ly49s+ NK cells in killing of target T cells. Thus, this CD8αα+MHC-II+ cell was a dually functional antigen presenting NK-like (AP-NK) cell. Following its coupling with target T cells through antigen presentation, killing stimulatory receptor Ly49s6 and co-receptor CD8αα on this cell used non-classic MHC-I RT1CE16 on the target T cells as a ligand to initiate killing. Thus, activated effector T cells with elevated expression of RT1CE16 were highly susceptible to the killing by the CD8αα+ AP-NK cell. Granule cytolytic perforin/granzyme C from this cell subsequently mediated cytotoxicity. Thus, inhibition of granzyme C effectively attenuated the killing. As it can recognize and eliminate effector autoreactive T cells in the inflamed target tissue, CD8αα+ AP-NK cell not only represents a new type of immune cell involved in immune tolerance, but also is a potential candidate for developing a cell-based therapy for pre-existing autoimmune diseases.
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DOI：
10.4049/jimmunol.0804333
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cai SF;Fehniger TA;Cao X;Mayer JC;Brune JD;French AR;Ley TJ
通讯作者：
Ley TJ
影响因子：
3.2
作者：
Roos, C;Walter, L
通讯作者：
Walter, L
影响因子：
4.4
作者：
Setiady, YY;Pramoonjago, P;Tung, KSK
通讯作者：
Tung, KSK
影响因子：
5.5
作者：
Kveberg, Lise;Jimenez-Royo, Pilar;Inngjerdingen, Marit
通讯作者：
Inngjerdingen, Marit
影响因子：
5.4
作者：
Bailey, NC;Kelly, CJ
通讯作者：
Kelly, CJ