Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease.
Direct Toll-like receptor 2 mediated co-stimulation of T cells in the mouse system as a basis for chronic inflammatory joint disease.
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DOI：
10.1186/ar1212
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发表时间：
2004
影响因子：
4.9
通讯作者：
Simon MM
中科院分区：
文献类型：
--
作者：
Sobek V;Birkner N;Falk I;Würch A;Kirschning CJ;Wagner H;Wallich R;Lamers MC;Simon MM
慢性炎症性关节疾病，如成人和青少年类风湿性关节炎和莱姆病的发病机制仍然知之甚少。在这方面的各种假设的中心是T细胞和B细胞的显著参与。在这里，我们提出了一个前提，即通过toll样受体(TLR)-2对预激活T细胞的名义抗原非依赖性多克隆激活在病原体诱导的慢性炎症性关节疾病的发生和延续中起关键作用。我们用以下证据来支持这一点。幼稚T细胞和效应T细胞都表达TLR-2。来自莱姆病病原伯氏疏螺旋体（Borrelia burgdorferi）的一种原型脂蛋白Lip-OspA，而不是其降解形式或脂多糖，能够通过TLR-2向抗原致敏的初始T细胞和细胞毒性T淋巴细胞（CTL）系提供直接的抗原非特异性共刺激信号。Lip-OspA诱导纯化的抗cd3致敏的C57BL/6小鼠的幼稚T细胞增殖和分泌干扰素(IFN)-γ，而tlr -2缺陷小鼠则没有。Lip-OspA对CTL细胞增殖和IFN-γ分泌的诱导不依赖于T细胞受体（TCR），但在TCR次激活后显著增强，并被抗TLR-2的单克隆抗体抑制。
The pathogenesis of chronic inflammatory joint diseases such as adult and juvenile rheumatoid arthritis and Lyme arthritis is still poorly understood. Central to the various hypotheses in this respect is the notable involvement of T and B cells. Here we develop the premise that the nominal antigen-independent, polyclonal activation of preactivated T cells via Toll-like receptor (TLR)-2 has a pivotal role in the initiation and perpetuation of pathogen-induced chronic inflammatory joint disease. We support this with the following evidence. Both naive and effector T cells express TLR-2. A prototypic lipoprotein, Lip-OspA, from the etiological agent of Lyme disease, namely Borrelia burgdorferi, but not its delipidated form or lipopolysaccharide, was able to provide direct antigen-nonspecific co-stimulatory signals to both antigen-sensitized naive T cells and cytotoxic T lymphocyte (CTL) lines via TLR-2. Lip-OspA induced the proliferation and interferon (IFN)-γ secretion of purified, anti-CD3-sensitized, naive T cells from C57BL/6 mice but not from TLR-2-deficient mice. Induction of proliferation and IFN-γ secretion of CTL lines by Lip-OspA was independent of T cell receptor (TCR) engagement but was considerably enhanced after suboptimal TCR activation and was inhibitable by monoclonal antibodies against TLR-2.
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影响因子：
56.9
作者：
Brightbill, HD;Libraty, DH;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
56.9
作者：
Aliprantis, AO;Yang, RB;Zychlinsky, A
通讯作者：
Zychlinsky, A
影响因子：
4.4
作者：
Hornung, V;Rothenfusser, S;Hartmann, G
通讯作者：
Hartmann, G
DOI：
10.1084/jem.186.5.757
发表时间：
1997-08-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Itoh Y;Germain RN
通讯作者：
Germain RN
影响因子：
158.5
作者：
HOOKS, JJ;MOUTSOPOULOS, HM;NOTKINS, AL
通讯作者：
NOTKINS, AL