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γ/δ T细胞在人无性细胞瘤和精原细胞瘤中的积聚:在自体肿瘤杀伤和肉芽肿形成中的作用。

Accumulation of gamma/delta T cells in human dysgerminoma and seminoma: roles in autologous tumor killing and granuloma formation.

作者信息

Zhao X, Wei Y Q, Kariya Y, Teshigawara K, Uchida A

机构信息

Department of Late Effect Studies, Kyoto University, Japan.

出版信息

Immunol Invest. 1995 May;24(4):607-18. doi: 10.3109/08820139509066861.

DOI:10.3109/08820139509066861
PMID:7622197
Abstract

The precise biological function of a subset of T cells bearing gamma/delta T cell receptor (TCR) remains poorly understood. The present study demonstrated the presence of gamma/delta T cells in tumor-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) of human patients with dysgerminoma and seminoma when determined by flow cytometry and in situ immunohistochemical staining. TIL contained a high percentage of gamma/delta T cells, ranging from 17.3 to 35.1%. gamma/delta T cells often accumulated within the granulomatous inflammation of tumor tissues. The majority of gamma/delta T cells were V gamma 9/V delta 2+ cells. Freshly isolated PBL, TIL and purified gamma/delta T cells showed autologous tumor killing (ATK) activity, which could be inhibited by monoclonal antibodies (mAb) against V delta 2. Furthermore, two gamma/delta T cell clones established from TIL showed cytotoxicity against autologous and allogeneic dysgerminoma, while they had low or no lytic effects on other cell types including carcinomas of ovary and tumor cell lines such as K562, Daudi and Molt-4. Lysis of autologous tumor cells by the clone was inhibited completely by anti-V delta 2 mAb and partially by mAb against CD3, LFA-1 alpha and ICAM-1 molecules, while it was resistant to anti-CD8, anti-HLA-ABC and anti-HLA-DR mAb. Supernatants produced by gamma/delta T cell clones induced adhesion, aggregation and increased DNA synthesis of monocytes and some characteristics of activated macrophages or epithelioid cells. Tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating factor (GM-CSF) and interferon (IFN)-gamma were detected in the supernatants of gamma/delta T cell clone. These results suggest that gamma/delta T cells accumulating in dysgerminoma and seminoma exhibit ATK activity through V gamma 9/delta 2 TCR and these gamma/delta T cells also play a role in the formation of granulomatous inflammation, which is associated with human dysgerminoma and seminoma.

摘要

携带γ/δ T细胞受体(TCR)的一部分T细胞的确切生物学功能仍知之甚少。本研究通过流式细胞术和原位免疫组织化学染色确定,在患有无性细胞瘤和精原细胞瘤的人类患者的肿瘤浸润淋巴细胞(TIL)和外周血淋巴细胞(PBL)中存在γ/δ T细胞。TIL中γ/δ T细胞的比例很高,范围为17.3%至35.1%。γ/δ T细胞常聚集在肿瘤组织的肉芽肿性炎症内。大多数γ/δ T细胞是Vγ9/Vδ2+细胞。新鲜分离的PBL、TIL和纯化的γ/δ T细胞显示出自体肿瘤杀伤(ATK)活性,这种活性可被抗Vδ2单克隆抗体(mAb)抑制。此外,从TIL建立的两个γ/δ T细胞克隆对自体和同种异体无性细胞瘤显示出细胞毒性,而它们对包括卵巢癌和肿瘤细胞系如K562、Daudi和Molt-4在内的其他细胞类型的裂解作用较低或没有。克隆对自体肿瘤细胞的裂解被抗Vδ2 mAb完全抑制,被抗CD3、LFA-1α和ICAM-1分子的mAb部分抑制,而它对抗CD8、抗HLA-ABC和抗HLA-DR mAb有抗性。γ/δ T细胞克隆产生的上清液诱导单核细胞的黏附、聚集并增加其DNA合成,以及激活巨噬细胞或上皮样细胞的一些特征。在γ/δ T细胞克隆的上清液中检测到肿瘤坏死因子(TNF)-α、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和干扰素(IFN)-γ。这些结果表明,在无性细胞瘤和精原细胞瘤中积累的γ/δ T细胞通过Vγ9/δ2 TCR表现出ATK活性,并且这些γ/δ T细胞在肉芽肿性炎症的形成中也起作用,这与人类无性细胞瘤和精原细胞瘤相关。

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