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超抗原通过诱导肿瘤细胞凋亡增加携带 T 细胞淋巴瘤的小鼠的存活率。

Superantigens increase the survival of mice bearing T cell lymphomas by inducing apoptosis of neoplastic cells.

机构信息

ILEX-CONICET, División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.

出版信息

PLoS One. 2010 Dec 22;5(12):e15694. doi: 10.1371/journal.pone.0015694.

Abstract

Superantigens bind to major histocompatibility complex class II molecules and interact with T cells expressing a particular T cell receptor Vβ inducing a strong proliferation/deletion response of the superantigen-reactive T cells. However, there have been no attempts to investigate the ability of Sags to induce apoptosis in neoplastic T cells by signaling through the Vβ region of their TCR. In the present study we show that bacterial and MMTV-encoded superantigens induce the apoptosis of AKR/J cognate lymphoma T cells both in vitro and in vivo. The Fas-Fas-L pathway was shown to be involved in the apoptosis of lymphoma T cells induced by bacterial superantigens. In vivo exposure to bacterial superantigens was able to improve the survival of lymphoma bearing mice. Moreover, the permanent expression of a retroviral encoded superantigen induced the complete remission of an aggressive lymphoma in a high percentage of mice. The possibility of a therapeutic use of superantigens in lymphoma/leukemia T cell malignancies is discussed.

摘要

超抗原与主要组织相容性复合体 II 类分子结合,并与表达特定 T 细胞受体 Vβ 的 T 细胞相互作用,诱导超抗原反应性 T 细胞的强烈增殖/删除反应。然而,目前还没有人试图通过 TCR 的 Vβ 区域的信号传导来研究 Sags 诱导肿瘤性 T 细胞凋亡的能力。在本研究中,我们表明细菌和 MMTV 编码的超抗原在体外和体内诱导 AKR/J 同源淋巴瘤 T 细胞的凋亡。 Fas-Fas-L 途径被证明参与了细菌超抗原诱导的淋巴瘤 T 细胞凋亡。体内暴露于细菌超抗原能够提高淋巴瘤荷瘤小鼠的存活率。此外,逆转录病毒编码的超抗原的永久表达诱导了高比例的小鼠侵袭性淋巴瘤的完全缓解。讨论了超抗原在淋巴瘤/白血病 T 细胞恶性肿瘤中的治疗用途的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07d3/3008744/636c78919d85/pone.0015694.g001.jpg

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