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IL-2/JES6-1 mAb 复合物通过 CD25Foxp3 T 细胞产生 IFN-γ，显著提高了对 LPS 的敏感性。

IL-2/JES6-1 mAb complexes dramatically increase sensitivity to LPS through IFN-γ production by CD25Foxp3 T cells.

机构信息

Laboratory of Tumor Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic.

Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic.

出版信息

Elife. 2021 Dec 21;10:e62432. doi: 10.7554/eLife.62432.

DOI:10.7554/eLife.62432
PMID:34932467
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8691839/
Abstract

Complexes of IL-2 and JES6-1 mAb (IL-2/JES6) provide strong sustained IL-2 signal selective for CD25 cells and thus they potently expand T cells. IL-2/JES6 are effective in the treatment of autoimmune diseases and in protecting against rejection of pancreatic islet allografts. However, we found that IL-2/JES6 also dramatically increase sensitivity to LPS-mediated shock in C57BL/6 mice. We demonstrate here that this phenomenon is dependent on endogenous IFN-γ and T cells, as it is not manifested in IFN-γ deficient and nude mice, respectively. Administration of IL-2/JES6 leads to the emergence of CD25Foxp3CD4 and CD25Foxp3CD8 T cells producing IFN-γ in various organs, particularly in the liver. IL-2/JES6 also increase counts of CD11bCD14 cells in the blood and the spleen with higher sensitivity to LPS in terms of TNF-α production and induce expression of CD25 in these cells. These findings indicate safety issue for potential use of IL-2/JES6 or similar IL-2-like immunotherapeutics.

摘要

IL-2 和 JES6-1 mAb 的复合物（IL-2/JES6）提供了针对 CD25 细胞的强持续 IL-2 信号，从而有效地扩增了 T 细胞。IL-2/JES6 可有效治疗自身免疫性疾病并防止胰岛同种异体移植物排斥。然而，我们发现 IL-2/JES6 还会显著增加 C57BL/6 小鼠对 LPS 介导的休克的敏感性。我们在此证明，这种现象依赖于内源性 IFN-γ 和 T 细胞，因为在 IFN-γ 缺陷和裸鼠中均未表现出这种现象。IL-2/JES6 的给药导致在各种器官中出现产生 IFN-γ 的 CD25Foxp3CD4 和 CD25Foxp3CD8 T 细胞，尤其是在肝脏中。IL-2/JES6 还增加了血液中 CD11bCD14 细胞的计数，并且在 TNF-α 产生方面，这些细胞对 LPS 的敏感性更高，并诱导这些细胞中 CD25 的表达。这些发现表明，对于潜在使用 IL-2/JES6 或类似的 IL-2 样免疫疗法存在安全性问题。

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