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感染志贺氏痢疾杆菌 1 型主要外膜蛋白后,通过白细胞介素-18 对 caspase-1 上调的 CD8(+)细胞进行选择性删除。

Selective deletion of CD8(+) cells upregulated by caspases-1 via IL-18 in mice immunized with major outer membrane protein of Shigella dysenteriae 1 following infection.

机构信息

Research & Development Division, Nutratech, Inc., Winnipeg, MB, R3Y 1M5, Canada.

出版信息

J Clin Immunol. 2010 May;30(3):408-18. doi: 10.1007/s10875-009-9359-8. Epub 2010 Jan 19.

Abstract

INTRODUCTION

Mucosal lymphoid changes were observed in cryopreserved rectal tissues obtained from BALB/c mice infected with Shigella dysenteriae 1, immunized with 57-kDa major antigenic outer membrane protein, and infection after immunization.

DISCUSSION

Our data suggested that caspase-3 is downregulated in CD4(+) cells of immunized BALB/c mice following infection with substantial increased expression of interleukin (IL)-2 and interferon (IFN)-gamma, while caspase-1 is upregulated in CD8(+) cells with decreased expression of IL-4 and IL-10. This indicated an involvement of Fas-mediated lytic pathway for selective deletion of CD8(+) cells out of CD3(+) T cells. IL-18 promotes inflammation and induces IFN-gamma and tumor necrosis factor (TNF)-alpha as the expression of IFN-gamma and TNF-alpha cytokines was evident in this study. It is assumed that the role of caspase-1 in inducing the CD4+ T cell activity increased with IL-18 rather than CD8+ suppressor cell activity. Bcl-2 is capable of inhibiting the Fas/Fas-L-mediated cell death for helper cells. Overall, the findings indicate that majority of the apoptotic cells were CD8(+) T cells in the groups of infection following immunization, and there might be a selective deletion of T lymphocytes mediated by caspase-1 via IL-18.

摘要

简介

在感染志贺氏痢疾杆菌 1 后,用 57kDa 主要抗原性外膜蛋白免疫的 BALB/c 小鼠的冷冻保存直肠组织中观察到黏膜淋巴样变化,并在感染后进行免疫。

讨论

我们的数据表明,感染后,免疫的 BALB/c 小鼠的 CD4+细胞中 caspase-3 下调,而白细胞介素(IL)-2 和干扰素(IFN)-γ的表达显著增加,而 caspase-1 在 CD8+细胞中上调,IL-4 和 IL-10 的表达降低。这表明 Fas 介导的裂解途径参与了 CD3+T 细胞中 CD8+细胞的选择性删除。IL-18 促进炎症,并诱导 IFN-γ 和肿瘤坏死因子(TNF)-α,因为本研究中明显表达了 IFN-γ 和 TNF-α细胞因子。可以假设,caspase-1 在诱导 CD4+T 细胞活性方面的作用随着 IL-18 而不是 CD8+抑制性细胞活性的增加而增加。Bcl-2 能够抑制 Fas/Fas-L 介导的辅助细胞死亡。总体而言,这些发现表明,在感染后免疫的组中,大多数凋亡细胞是 CD8+T 细胞,并且可能存在由 caspase-1 通过 IL-18 介导的 T 淋巴细胞的选择性删除。

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