Mizrahi Sa'ar, Yefenof Eitan, Gross Menahem, Attal Pierre, Ben Yaakov Avraham, Goldman-Wohl Debra, Maly Bella, Stern Noam, Katz Gil, Gazit Roi, Sionov Ronit Vogt, Mandelboim Ofer, Chaushu Stella
Lautenberg Center of General and Tumor Immunology, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
J Leukoc Biol. 2007 Nov;82(5):1095-105. doi: 10.1189/jlb.0407205. Epub 2007 Aug 3.
Adenoids are part of the MALT. In the present study, we analyzed cell surface markers and cytolytic activity of adenoidal NK (A-NK) cells and compared them with NK cells derived from blood of the same donors (B-NK). NK cells comprised 0.67% (0.4-1.2%) of the total lymphoid population isolated from adenoids. The majority (median=92%) of the A-NK cells was CD56(bright)CD16(-). A-NK cells were characterized by the increased expression of activation-induced receptors. NKp44 was detected on >60%, CD25 on >40%, and HLA-DR on >50% of freshly isolated A-NK cells. Functional assays indicated that the cytotoxic machinery of A-NK is intact, and sensitive target cells are killed via natural cytotoxicity receptors, such as NKG2D. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1; CD66) expression was up-regulated in 23% (median) of the A-NK cells by IL-2 activation but unchanged in B-NK cells. CEACAM1 inhibited the A-NK killing of target cells. CXCR4 was expressed on more than 40% A-NK cells prior to activation. Its ligand, CXCL12, was found in endothelial cells of the capillaries within the adenoid and in cells of the epithelial lining. In addition, A-NK cells migrated in vitro toward a gradient of CXCL12 in a dose-responsive manner, suggesting a role for this chemokine in A-NK cell recruitment and trafficking. We conclude that the A-NK cells are unique in that they display an activated-like phenotype and are different from their CD16(-) B-NK cell counterparts. This phenotype presumably reflects the chronic interaction of A-NK cells with antigens penetrating the body through the nasal route.
腺样体是黏膜相关淋巴组织（MALT）的一部分。在本研究中，我们分析了腺样体自然杀伤（A-NK）细胞的细胞表面标志物和细胞溶解活性，并将它们与来自相同供体血液的自然杀伤（B-NK）细胞进行比较。自然杀伤细胞占从腺样体分离的总淋巴细胞群体的0.67%（0.4 - 1.2%）。大多数（中位数 = 92%）的A-NK细胞为CD56（明亮型）CD16（阴性）。A-NK细胞的特征是激活诱导受体的表达增加。在新鲜分离的A-NK细胞中，超过60%检测到NKp44，超过40%检测到CD25，超过50%检测到HLA-DR。功能分析表明，A-NK的细胞毒性机制是完整的，敏感靶细胞通过自然细胞毒性受体如NKG2D被杀伤。癌胚抗原相关细胞黏附分子1（CEACAM1；CD66）的表达在23%（中位数）的A-NK细胞中通过白细胞介素-2激活而上调，但在B-NK细胞中无变化。CEACAM1抑制A-NK对靶细胞的杀伤。CXCR4在激活前在超过40%的A-NK细胞上表达。其配体CXCL12在腺样体毛细血管的内皮细胞和上皮衬里细胞中被发现。此外，A-NK细胞在体外以剂量反应方式向CXCL12梯度迁移，表明该趋化因子在A-NK细胞募集和运输中起作用。我们得出结论，A-NK细胞的独特之处在于它们表现出类似激活的表型，并且与其CD16（阴性）的B-NK细胞对应物不同。这种表型可能反映了A-NK细胞与通过鼻腔途径侵入人体的抗原的慢性相互作用。
