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辅助性T1细胞发育的一种不依赖信号转导及转录激活因子4（Stat4）的途径。

A signal transducer and activator of transcription (Stat)4-independent pathway for the development of T helper type 1 cells.

作者信息

Kaplan M H, Wurster A L, Grusby M J

机构信息

Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

出版信息

J Exp Med. 1998 Sep 21;188(6):1191-6. doi: 10.1084/jem.188.6.1191.

DOI:10.1084/jem.188.6.1191
PMID:9743537
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2212539/
Abstract

The differentiation of T helper (Th) cells is regulated by members of the signal transducer and activator of transcription (STAT) family of signaling molecules. We have generated mice lacking both Stat4 and Stat6 to examine the ability of Th cells to develop in the absence of these two transcription factors. Stat4, Stat6(-/-) lymphocytes fail to differentiate into interleukin (IL)-4-secreting Th2 cells. However, in contrast to Stat4(-/-) lymphocytes, T cells from Stat4, Stat6(-/-) mice produce significant amounts of interferon (IFN)-gamma when activated in vitro. Although Stat4, Stat6(-/-) lymphocytes produce less IFN-gamma than IL-12-stimulated control lymphocytes, equivalent numbers of IFN-gamma-secreting cells can be generated from cultures of Stat4, Stat6(-/-) lymphocytes activated under neutral conditions and control lymphocytes activated under Th1 cell-promoting conditions. Moreover, Stat4, Stat6(-/-) mice are able to mount an in vivo Th1 cell-mediated delayed-type hypersensitivity response. These results support a model of Th cell differentiation in which the generation of Th2 cells requires Stat6, whereas a Stat4-independent pathway exists for the development of Th1 cells.

摘要

辅助性T（Th）细胞的分化受信号转导及转录激活蛋白（STAT）信号分子家族成员的调控。我们构建了同时缺失Stat4和Stat6的小鼠，以研究在缺乏这两种转录因子的情况下Th细胞的发育能力。Stat4、Stat6（-/-）淋巴细胞无法分化为分泌白细胞介素（IL）-4的Th2细胞。然而，与Stat4（-/-）淋巴细胞不同，来自Stat4、Stat6（-/-）小鼠的T细胞在体外激活时会产生大量干扰素（IFN）-γ。虽然Stat4、Stat6（-/-）淋巴细胞产生的IFN-γ比IL-12刺激的对照淋巴细胞少，但在中性条件下激活的Stat4、Stat6（-/-）淋巴细胞培养物和在Th1细胞促进条件下激活的对照淋巴细胞培养物能产生等量的分泌IFN-γ的细胞。此外，Stat4、Stat6（-/-）小鼠能够产生体内Th1细胞介导的迟发型超敏反应。这些结果支持了一种Th细胞分化模型，即Th2细胞的产生需要Stat6，而Th1细胞的发育存在一条不依赖Stat4的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/56d77d9c57e5/JEM980386.f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/4e6e7ab2d9aa/JEM980386.f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/7fefb21e4a32/JEM980386.f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/a47d9e7deb12/JEM980386.f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/56d77d9c57e5/JEM980386.f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/4e6e7ab2d9aa/JEM980386.f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/7fefb21e4a32/JEM980386.f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/a47d9e7deb12/JEM980386.f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/234c/2212539/56d77d9c57e5/JEM980386.f4.jpg

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1
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Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10838-43. doi: 10.1073/pnas.94.20.10838.
2
Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells.人辅助性T细胞2亚群对嗜酸性粒细胞趋化因子受体CCR3的选择性表达。
Science. 1997 Sep 26;277(5334):2005-7. doi: 10.1126/science.277.5334.2005.
3
Characterization of IL-12 receptor beta1 chain (IL-12Rbeta1)-deficient mice: IL-12Rbeta1 is an essential component of the functional mouse IL-12 receptor.
STAT4 在全身性红斑狼疮样自身免疫和外来抗原驱动的抗体形成细胞、生发中心和滤泡辅助性 T 细胞反应中基本可有可无。
Immunohorizons. 2021 Jan 14;5(1):2-15. doi: 10.4049/immunohorizons.2000111.
4
Recent advances in the clinical development of immune checkpoint blockade therapy.免疫检查点阻断疗法的临床开发进展。
Cell Oncol (Dordr). 2019 Oct;42(5):609-626. doi: 10.1007/s13402-019-00456-w. Epub 2019 Jun 14.
5
Cancer immunoediting and resistance to T cell-based immunotherapy.癌症免疫编辑与 T 细胞免疫疗法抵抗。
Nat Rev Clin Oncol. 2019 Mar;16(3):151-167. doi: 10.1038/s41571-018-0142-8.
6
Mechanisms of Resistance to PD-1 and PD-L1 Blockade.对PD-1和PD-L1阻断的耐药机制。
Cancer J. 2018 Jan/Feb;24(1):47-53. doi: 10.1097/PPO.0000000000000303.
7
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.癌症免疫疗法的原发性、适应性和获得性耐药性。
Cell. 2017 Feb 9;168(4):707-723. doi: 10.1016/j.cell.2017.01.017.
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白细胞介素-12受体β1链（IL-12Rβ1）缺陷小鼠的特征：IL-12Rβ1是功能性小鼠白细胞介素-12受体的重要组成部分。
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4
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J Exp Med. 1997 Mar 3;185(5):817-24. doi: 10.1084/jem.185.5.817.
5
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Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3189-94. doi: 10.1073/pnas.94.7.3189.
6
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J Exp Med. 1997 Feb 3;185(3):573-8. doi: 10.1084/jem.185.3.573.
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Nature. 1997 Jan 2;385(6611):81-3. doi: 10.1038/385081a0.
8
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Nature. 1996 Oct 31;383(6603):787-93. doi: 10.1038/383787a0.
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