Dysregulation of regulatory CD56bright NK cells/T cells interactions in multiple sclerosis
Dysregulation of regulatory CD56bright NK cells/T cells interactions in multiple sclerosis
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DOI：
10.1016/j.jaut.2016.04.003
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发表时间：
2016-08-01
影响因子：
12.8
通讯作者：
Uccelli, Antonio
中科院分区：
文献类型：
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作者：
Laroni, Alice;Armentani, Eric;Uccelli, Antonio
最近的证据表明，CD56(bright) NK 细胞是淋巴结中丰富的 NK 细胞的一个子集，可能具有免疫调节功能。在多发性硬化症 (MS) 中，CD56(bright) NK 细胞的扩增与对不同治疗的成功反应以及妊娠期间疾病的缓解有关；它们是否在生理条件下发挥免疫调节作用以及免疫调节在多发性硬化症中是否受到损害尚不清楚。我们剖析了 CD56(bright) NK 细胞在健康受试者 (HS) 中的免疫调节作用，并将其与未经治疗的 MS 受试者或患有提示 MS 的临床孤立综合征 (CIS) 的患者进行了比较。我们发现来自 HS 的 CD56(bright) NK 细胞在炎症信号下获得了通过直接细胞毒性抑制自体 CD4+T 细胞增殖的能力，这需要天然细胞毒性受体 (NCR) 的参与和颗粒酶 B 的分泌。来自 MS/CIS 患者的 CD56(bright) NK 细胞在频率上没有差异，并且具有相似的表型，但表现出明显较低的抑制自体 T 细胞增殖的能力。这种损伤与 CD56(bright) NK 细胞 NCR 或颗粒酶 B 的表达缺陷无关，而是与 MS/CIS 受试者的 T 细胞上 HLA-E 表达增加有关，这可能增强由在 CD56(bright) NK 细胞上均匀表达的 NKG2A 介导的抑制作用。 MS/CIS 中 CD56(bright) NK 细胞控制自体 T 细胞的缺陷可能导致与疾病发展相关的过度自身免疫反应。 (C) 2016 年作者。由爱思唯尔有限公司出版
Recent evidence has shown that CD56(bright) NK cells, a subset of NK cells abundant in lymph nodes, may have an immunoregulatory function. In multiple sclerosis (MS), expansion of CD56(bright) NK cells has been associated to successful response to different treatments and to remission of disease during pregnancy; how whether they exert immunoregulation in physiologic conditions and whether this is impaired in MS is not known. We dissected the immunoregulatory role of CD56(bright) NK cells function in healthy subjects (HS) and compared it with that of untreated MS subjects or patients with clinically isolated syndrome suggestive of MS (CIS). We found that CD56(bright) NK cells from HS acquire, upon inflammatory cues, the capability of suppressing autologous CD4+T cell proliferation through direct cytotoxicity requiring engagement of natural cytotoxicity receptors (NCRs) and secretion of granzyme B. CD56(bright) NK cells from patients with MS/CIS did not differ in frequency and share a similar phenotype but displayed a significantly lower ability to inhibit autologous T cell proliferation. This impairment was not related to deficient expression of NCRs or granzyme B by CD56(bright) NK cells, but to increased HLA-E expression on T cells from MS/CIS subjects, which could enhance the inhibitory effect mediated by NKG2A that is homogeneously expressed on CD56(bright) NK cells. The defect in controlling autologous T cells by CD56(bright) NK cells in MS/CIS might contribute to the excess of autoimmune response that is associated to disease development. (C) 2016 The Authors. Published by Elsevier Ltd.