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维甲酸诱导CD1d表达使慢性淋巴细胞白血病B细胞致敏,以被CD8不变自然杀伤T细胞杀伤。

Retinoic acid induction of CD1d expression primes chronic lymphocytic leukemia B cells for killing by CD8 invariant natural killer T cells.

作者信息

Ghnewa Yasmeen G, O'Reilly Vincent P, Vandenberghe Elisabeth, Browne Paul V, McElligott Anthony M, Doherty Derek G

机构信息

Department of Immunology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland.

Department of Haematology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland; Department of Haematology, St. James's Hospital, Dublin, Ireland.

出版信息

Clin Immunol. 2017 Oct;183:91-98. doi: 10.1016/j.clim.2017.08.002. Epub 2017 Aug 3.

Abstract

Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5. Retinoic acid receptor-α (RAR-α) agonists induced CD1d expression by CLL B cells, restoring their ability to present α-GalCer to CD8α iNKT cells, resulting in cytolytic degranulation. Thus, RAR-α agonists can augment the anti-tumor activities of iNKT cells against CLL cells in vitro. Their inclusion in iNKT cell-based therapies may benefit patients with CLL.

摘要

不变自然杀伤T(iNKT)细胞是对CD1d呈递的糖脂抗原产生应答的细胞毒性T细胞。用α-半乳糖神经酰胺(α-GalCer)对iNKT细胞进行治疗性激活可预防和逆转小鼠肿瘤生长,涉及α-GalCer刺激的iNKT细胞的临床试验正在人类中进行。B细胞表达CD1d,然而,我们发现慢性淋巴细胞白血病(CLL)患者B细胞上的CD1d表达降低。用α-GalCer脉冲处理的CLL患者B细胞未能刺激iNKT细胞系进行溶细胞脱颗粒,但可呈递更强效的糖脂类似物7DW8-5。维甲酸受体-α(RAR-α)激动剂可诱导CLL B细胞表达CD1d,恢复其将α-GalCer呈递给CD8α iNKT细胞的能力,从而导致溶细胞脱颗粒。因此,RAR-α激动剂可在体外增强iNKT细胞对CLL细胞的抗肿瘤活性。将它们纳入基于iNKT细胞的疗法可能会使CLL患者受益。

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