Dulphy Nicolas, Berrou Jeannig, Campillo José A, Bagot Martine, Bensussan Armand, Toubert Antoine
Institut National de la Santé et de la Recherche Médicale U662, Institut Universitaire d'Hématologie, Centre Hayem, Hôpital Saint-Louis, Paris, France.
J Invest Dermatol. 2009 Feb;129(2):359-64. doi: 10.1038/jid.2008.256. Epub 2008 Aug 28.
Sezary syndrome (SS) is a rare lymphoma characterized by the clonal expansion in the skin and in blood of CD4(+)CD158k(+) T cells. Natural killer (NK) activation against tumors in leukemia models is partly based on the recognition of the target through the NKG2D/NKG2D ligands interactions. We analyzed ex vivo SS malignant lymphocytes for the expression of the NKG2D ligands such as the major histocompatibility complex class I-related molecules (MIC) A and B and the UL16 binding proteins (ULBP). The expressions of NKG2D, the natural cytotoxicity receptors (NKp30, NKp44, and NKp46) and the activating receptor DNAM-1 were simultaneously investigated on circulating patients NK and CD8(+) nonmalignant lymphocytes. Interestingly, although at least one of the NKG2D ligands was expressed on the circulating malignant lymphocytes of 9 out of 10 patients, NKG2D was expressed on effector lymphocytes. We found that soluble MICA in patient's sera was increased, which may constitute a mechanism to escape the immune response. In vitro, SS tumor lymphocytes induced the degranulation of perforin by the NKL cell line. More importantly, NKG2D expressed on SS patients NK cells is functional and capable to induce degranulation. Altogether, these data could suggest that stimulating NK function in SS patients may be a promising strategy to reduce tumor invasion.
塞扎里综合征（SS）是一种罕见的淋巴瘤，其特征为CD4(+)CD158k(+) T细胞在皮肤和血液中的克隆性扩增。在白血病模型中，自然杀伤（NK）细胞对肿瘤的激活部分基于通过NKG2D/NKG2D配体相互作用对靶标的识别。我们分析了体外SS恶性淋巴细胞中NKG2D配体的表达情况，如主要组织相容性复合体I类相关分子（MIC）A和B以及UL16结合蛋白（ULBP）。同时研究了循环患者NK细胞和CD8(+)非恶性淋巴细胞上NKG2D、自然细胞毒性受体（NKp30、NKp44和NKp46）以及激活受体DNAM-1的表达。有趣的是，尽管10名患者中有9名患者的循环恶性淋巴细胞上表达了至少一种NKG2D配体，但效应淋巴细胞上也表达了NKG2D。我们发现患者血清中的可溶性MICA增加，这可能构成逃避免疫反应的一种机制。在体外，SS肿瘤淋巴细胞可诱导NKL细胞系的穿孔素脱颗粒。更重要的是，SS患者NK细胞上表达的NKG2D具有功能，能够诱导脱颗粒。总之，这些数据表明刺激SS患者的NK功能可能是减少肿瘤侵袭的一种有前景的策略。
