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首页> 外文期刊>Infection and immunity >Critical Contribution of CD28-CD80/CD86 Costimulatory Pathway to Protection from Trypanosoma cruzi Infection
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Critical Contribution of CD28-CD80/CD86 Costimulatory Pathway to Protection from Trypanosoma cruzi Infection

机译：CD28-CD80 / CD86共刺激途径对克氏锥虫感染的保护作用的关键贡献

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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.
机译：CD28-CD80 / CD86介导的T细胞共刺激途径已被可变地牵涉到传染性免疫中。在这项研究中，我们通过使用CD28缺陷型小鼠和阻断针对CD80和CD86的抗体，研究了这种共刺激途径在抵抗克氏锥虫感染中的作用。 CD28缺陷小鼠表现出明显加剧的 T。狂犬病无情的寄生虫病和野生型小鼠非致命剂量感染后100％的死亡率证明了克鲁兹病的发生。通过施用特异性单克隆抗体对CD80和CD86的阻断也加剧了 T。野生型小鼠中的cruzi 感染。来自 T的脾细胞。感染了cruzi 的CD28缺陷小鼠表现出对 T的强烈干扰。与感染的野生型小鼠相比，cruzi 抗原的体外刺激性更高。 T的诱导。 Crum 抗原特异性CD8 + T细胞在 T中也受损。感染了cruzi 的CD28缺陷小鼠。除了这些缺陷之外，天然抗 T的能力也很强。在Cruzi 感染中，CD28缺陷型小鼠在诱导CD8 + -T细胞介导的针对 T的保护性免疫方面也存在缺陷。 DNA疫苗可感染cruzi 。这些结果首次证明了CD28-CD80 / CD86共刺激途径的重要贡献，不仅对自然保护抵抗初级 T。 Cruzi 感染，而且还感染了DNA疫苗诱导的恰加斯氏病的保护性免疫。

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