Monocytes enhance cell proliferation and LMP1 expression of nasal natural killer/T-cell lymphoma cells by cell contact-dependent interaction through membrane-bound IL-15
Monocytes enhance cell proliferation and LMP1 expression of nasal natural killer/T-cell lymphoma cells by cell contact-dependent interaction through membrane-bound IL-15
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DOI：
10.1002/ijc.25969
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发表时间：
2012-01-01
影响因子：
6.4
通讯作者：
Klein, Eva
中科院分区：
文献类型：
--
作者：
Ishii, Hideyuki;Takahara, Miki;Klein, Eva
鼻自然杀伤（NK）/T细胞淋巴瘤（NNKTL）是一种与EB病毒（EBV）相关的恶性肿瘤，预后差，具有独特的组织学特征，其特征在于血管中心性和多形淋巴网状浸润，包括炎性细胞，如粒细胞、单核细胞、巨噬细胞和淋巴细胞。在这里，我们表明，单核细胞通过细胞接触依赖性相互作用，通过膜结合的白细胞介素（IL）-15增强增殖以及LMP 1表达的NNKTL细胞。我们使用了两种EBV阳性NK细胞系，SNK 6和KAI 3，它们来源于两名患者-SNK 6来自患有NNKTL的患者，KAI 3来自患有严重蚊子过敏的患者。我们将细胞系与粒细胞或单核细胞共培养，并检查细胞的增殖、存活和LMP 1表达是否发生变化。虽然共培养的粒细胞不影响细胞的增殖，存活或LMP 1表达，但共培养的单核细胞以剂量依赖性方式增强增殖和LMP 1表达。当单核细胞被放置在单独的室中时，未观察到这些现象。此外，单核细胞诱导的增殖和LMP 1的表达抑制治疗与IL-15的抗体。此外，干扰素-γ-诱导蛋白（IP）-10的产生通过与单核细胞共培养而增强，并被抗体抑制。免疫组织学研究证实，在所有20个NNKTL组织中，大量浸润的CD 14阳性单核细胞与CD 56阳性淋巴瘤细胞接触。这些结果表明，单核细胞通过膜结合IL-15通过细胞接触依赖性相互作用增强NNKTL细胞的细胞生长以及LMP 1表达。在NNKTL组织的微环境中，淋巴瘤细胞和单核细胞之间相互作用的正反馈回路可能存在并有助于淋巴瘤进展。
Nasal natural killer (NK)/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-related malignancy with poor prognosis and has distinct histological features characterized by angiocentric and polymorphous lymphoreticular infiltrates including inflammatory cells such as granulocytes, monocytes, macrophages and lymphocytes. Here, we show that the monocytes enhance proliferation as well as LMP1 expression of NNKTL cells by cell contact-dependent interaction through membranebound interleukin (IL)-15. We used two EBV-positive NK-cell lines, SNK6 and KAI3, which originated from two patients-SNK6 from a patient with NNKTL and KAI3 from a patient with a severe mosquito allergy. We cocultured the cell lines with granulocytes or monocytes and examined whether proliferation, survival and LMP1 expression of the cells changed. Although cocultured granulocytes did not affect proliferation, survival or LMP1 expression of the cells, cocultured monocytes enhanced both proliferation and LMP1 expression in a dose-dependent manner. These phenomena were not seen when monocytes were placed in a separate chamber. Moreover, the monocyte-inducible proliferation and LMP1 expression were inhibited by treatment with an antibody against IL-15. Furthermore, production of interferon-gamma-inducible protein (IP)-10 were enhanced by coculture with monocytes and were inhibited by the antibody. Immunohistological studies confirmed that a number of infiltrating CD14-positive monocytes contacted CD56-positive lymphoma cells in all of 20 NNKTL tissues tested. These results suggest that monocytes enhance cell growth as well as LMP1 expression of NNKTL cells by cell contactdependent interaction through membrane-bound IL-15. In the microenvironment of NNKTL tissue, a positive feedback loop of interaction between lymphoma cells and monocytes may be present and contribute to lymphoma progression.