Critical contribution of CD28-CD80/CD86 costimulatory pathway to protection from Trypanosoma cruzi infection
Critical contribution of CD28-CD80/CD86 costimulatory pathway to protection from Trypanosoma cruzi infection
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DOI：
10.1128/iai.71.6.3131-3137.2003
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发表时间：
2003-06-01
影响因子：
3.1
通讯作者：
Aoki, T
中科院分区：
文献类型：
--
作者：
Miyahira, Y;Katae, M;Aoki, T
CD 28-CD 80/CD 86介导的T细胞共刺激途径已被证实参与感染性免疫。在这项研究中，我们研究了这种共刺激途径的作用，抗克氏锥虫感染，使用CD 28缺陷型小鼠和阻断抗体CD 80和CD 86。CD 28缺陷小鼠T. Cruzi感染，如通过在野生型小鼠中用非致死剂量感染后持续的寄生虫血症和100%死亡率所证明的。通过施用特异性单克隆抗体阻断CD 80和CD 86也加重了T。野生型小鼠中的克氏感染。T. Cruzi感染的CD 28缺陷小鼠对T.与来自感染的野生型小鼠的那些相比，体外的Cruzi抗原刺激。T. T细胞中cruzi抗原特异性CD 8（+）T细胞也受损。克氏病毒感染的CD 28缺陷小鼠。除了自然保护方面的这些缺陷外，CD 28缺陷型小鼠在诱导CD 8（+）-T细胞介导的抗T.克氏病毒感染的DNA疫苗。这些结果第一次证明了CD 28-CD 80/CD 86共刺激通路不仅对抗原发性T细胞的天然保护作用，Cruzi感染，而且DNA疫苗诱导的对恰加斯病的保护性免疫。
The CD28-CD80/CD86-mediated T-cell costimulatory pathway has been variably implicated in infectious immunity. In this study, we investigated the role of this costimulatory pathway in resistance to Trypanosoma cruzi infection by using CD28-deficient mice and blocking antibodies against CD80 and CD86. CD28-deficient mice exhibited markedly exacerbated T. cruzi infection, as evidenced by unrelenting parasitemia and 100% mortality after infection with doses that are nonlethal in wild-type mice. The blockade of both CD80 and CD86 by administering specific monoclonal antibodies also exacerbated T. cruzi infection in wild-type mice. Splenocytes from T. cruzi-infected, CD28-deficient mice exhibited greatly impaired gamma interferon production in response to T. cruzi antigen stimulation in vitro compared to those from infected wild-type mice. The induction of T. cruzi antigen-specific CD8(+) T cells was also impaired in T. cruzi-infected, CD28-deficient mice. In addition to these defects in natural protection against T. cruzi infection, CD28-deficient mice were also defective in the induction of CD8(+)-T-cell-mediated protective immunity against T. cruzi infection by DNA vaccination. These results demonstrate, for the first time, a critical contribution of the CD28-CD80/CD86 costimulatory pathway not only to natural protection against primary T. cruzi infection but also to DNA vaccine-induced protective immunity to Chagas' disease.