Pertussis toxin-induced cytokine differentiation and clonal expansion of T cells is mediated predominantly via costimulation
Pertussis toxin-induced cytokine differentiation and clonal expansion of T cells is mediated predominantly via costimulation
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DOI：
10.1016/j.cellimm.2007.05.004
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发表时间：
2007-03-01
影响因子：
4.3
通讯作者：
Forsthuber, Thomas G.
中科院分区：
文献类型：
--
作者：
Denkinger, Claudia M.;Denkinger, Michael D.;Forsthuber, Thomas G.
百日咳毒素（PTX）在体内具有强大的免疫佐剂活性，并同时增强T辅助型（Th1）和Th2细胞因子反应。ptx诱导的thi和Th2免疫增强是通过激活抗原呈递细胞（APCs）介导的，但其潜在机制尚不清楚。在这里，我们询问PTX对T细胞免疫的佐剂活性是否由细胞因子和/或共刺激信号介导。结果表明，体内阻断CD28-CD80/86共刺激基本上可以消除ptx介导的抗原特异性Th1和Th2反应的增强。阻断CD40L-CD40相互作用在抑制ptx介导的Th1和Th2反应增强方面效率较低。相比之下，PTX的佐剂活性不是通过细胞因子介导的，因为在缺乏IL-12、ifn - γ、IL-4、IL-5或IL-6的小鼠中，Th1和Th2的反应都没有明显受损。综上所述，这些数据表明PTX通过调节apc上的共刺激分子介导其对T细胞细胞因子分化和克隆扩增的辅助作用。了解PTX靶向的共刺激途径可以设计出选择性诱导Th1或Th2免疫的新型佐剂。(C) 2007爱思唯尔公司版权所有。
Pertussis toxin (PTX) has potent immunologic adjuvant activity in vivo and concomitantly enhances both T helper type (Th1) and Th2 cytokine responses. The PTX-induced enhancement of Th I and Th2 immunity is mediated via the activation of antigen presenting cells (APCs), but the underlying mechanism is not known. Here we asked whether the adjuvant activity of PTX on T cell immunity was mediated by cytokines and/or costimulatory signals. The results show that in vivo blockade of CD28-CD80/86 costimulation essentially abrogated PTX-mediated enhancement of antigen-specific Th1 and Th2 responses. Blockade of CD40L-CD40 interactions was less efficient in inhibiting PTX-mediated enhancement of Th1 and Th2 responses. In contrast, the adjuvant activity of PTX was not mediated via cytokines, because neither Th1 nor Th2 responses were substantially impaired in mice deficient for IL-12, IFN-gamma, IL-4, IL-5, or IL-6. Collectively, the data suggest that PTX mediates its adjuvant effects on T cell cytokine differentiation and clonal expansion via the modulation of costimulatory molecules on APCs. Understanding the costimulatory pathways targeted by PTX could lead to the design of novel adjuvants that selectively induce Th1 or Th2 immunity. (C) 2007 Elsevier Inc. All rights reserved.