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石棉暴露对人外周血单个核细胞混合淋巴细胞反应中细胞毒性 T 淋巴细胞分化的影响。

Effect of asbestos exposure on differentiation of cytotoxic T lymphocytes in mixed lymphocyte reaction of human peripheral blood mononuclear cells.

机构信息

Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan.

出版信息

Am J Respir Cell Mol Biol. 2013 Jul;49(1):28-36. doi: 10.1165/rcmb.2012-0134OC.

Abstract

Asbestos fibers are associated with tumorigenicity, and are thought to cause mesothelioma. However, their effect on immune response remains unclear. We examined the effect of asbestos exposure on differentiation of cytotoxic T lymphocytes (CTLs) in mixed lymphocyte reactions (MLR) of human peripheral blood mononuclear cells (PBMCs) upon exposure to chrysotile B (CB) or crocidolite (CR) asbestos at 5 μg/ml for 7 days. Exposure to CB during MLR suppressed increases in the percentage and number of CD8⁺ T cells in response to allogenic cells. The cytotoxicity for allogenic targets decreased in PBMCs exposed to CB, but not CR, when compared with PBMCs without any exposure during MLR. Exposure to CB during MLR resulted in suppression of increases in granzyme B⁺ cells and IFN-γ⁺ cells. CB exposure also resulted in suppression of increases in CD45RO⁺ effector/memory cells and CD25⁺-activated cells in CD8⁺ lymphocytes, and a decrease in CD45RA⁺ cells. CB exposure suppressed the proliferation of CD8⁺ lymphocytes without an increase in annexin V⁺ apoptotic cells in CD8⁺ lymphocytes. Moreover, the production of IL-10, IFN-γ, and TNF-α, but not IL-2, decreased in the presence of CB. These results suggest that exposure to asbestos potentially suppresses the differentiation of cytotoxic T lymphocyte, accompanied by decreases in IFN-γ and TNF-α.

摘要

石棉纤维与肿瘤形成有关,被认为会导致间皮瘤。然而,它们对免疫反应的影响尚不清楚。我们研究了在混合淋巴细胞反应(MLR)中,人外周血单核细胞(PBMC)暴露于 5μg/ml 的温石棉 B(CB)或青石棉(CR)7 天后,石棉暴露对细胞毒性 T 淋巴细胞(CTL)分化的影响。在 MLR 中暴露于 CB 会抑制对同种异体细胞反应的 CD8⁺T 细胞百分比和数量的增加。与 MLR 中未暴露于 CB 的 PBMC 相比,暴露于 CB 的 PBMC 对同种异体靶细胞的细胞毒性降低。在 MLR 中暴露于 CB 会抑制颗粒酶 B⁺细胞和 IFN-γ⁺细胞的增加。CB 暴露还会抑制 CD8⁺淋巴细胞中 CD45RO⁺效应/记忆细胞和 CD25⁺激活细胞的增加,并降低 CD45RA⁺细胞。CB 暴露抑制 CD8⁺淋巴细胞的增殖,而不会增加 CD8⁺淋巴细胞中 Annexin V⁺凋亡细胞。此外,在存在 CB 的情况下,IL-10、IFN-γ 和 TNF-α的产生减少,而 IL-2 则没有增加。这些结果表明,暴露于石棉可能会抑制细胞毒性 T 淋巴细胞的分化,同时降低 IFN-γ 和 TNF-α 的产生。

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