Murine Malaria Is Exacerbated by CTLA-4 Blockade1
Murine Malaria Is Exacerbated by CTLA-4 Blockade1
复制标题
CTLA-4 封锁加剧了小鼠疟疾1
作者：
T. Jacobs;S. Graefe;Sonja Niknafs;Iris Gaworski;B. Fleischer
溶细胞 T 淋巴细胞相关 Ag-4 (CD152) 是一种负调节分子，主要在 T 细胞激活后表达。在这项研究中，我们研究了 CTLA-4 表达在实验性血期疟疾中的作用。与人类疟疾类似，感染伯氏疟原虫后，C57BL/6 小鼠的 CD4+ T 细胞上表达 CTLA-4。动力学分析显示，CTLA-4 表达在感染后第 5 天增加，并在感染后第 9 天达到峰值，此时几乎 10% 的脾 CD4+ T 细胞表达 CTLA-4。通过特定的单克隆抗体在体内阻断 CTLA-4 并随后用伯氏疟原虫进行攻击，会引起让人想起小鼠脑型疟疾和早期死亡的神经系统症状。对抗 CTLA-4 治疗小鼠脑切片的组织学检查显示出出血和水肿等病理变化，而对照组小鼠则没有这些变化。此外，抗 CTLA-4 治疗还逆转了血期疟疾期间 CD4+ T 细胞的大量损失和 T 细胞反应的抑制。我们的数据表明，CTLA-4 表达通过限制疟疾期间 T 细胞的激活来预防免疫病理。他们还表明，脑型疟疾的发生是由于未能下调 T 细胞活化而介导的。
Cytolytic T lymphocyte-associated Ag-4 (CD152) is a negatively regulating molecule, which is primarily expressed on T cells following their activation. In this study, we have examined the role of CTLA-4 expression in experimental blood-stage malaria. Similar to human malaria, CTLA-4 is expressed on CD4+ T cells of C57BL/6 mice after infection with Plasmodium berghei. A kinetic analysis revealed that CTLA-4 expression was increased on day 5 postinfection and reached a peak on day 9 postinfection, when almost 10% of splenic CD4+ T cells expressed CTLA-4. Blockade of CTLA-4 in vivo by a specific mAb and subsequent challenge with P. berghei caused neurological signs reminiscent of murine cerebral malaria and earlier death. Histologic examination of brain sections from anti-CTLA-4-treated mice revealed pathologic changes such as hemorrhages and edema, which were absent in control mice. Furthermore, treatment with anti-CTLA-4 also reversed the extensive loss of CD4+ T cells and the suppressed T cell response occurring during blood-stage malaria. Our data suggest that CTLA-4 expression prevents immune pathology by restricting T cell activation during malaria. They also indicate that the development of cerebral malaria is mediated by a failure to down-regulate T cell activation.
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影响因子：
4.4
作者：
H. Shear;R. Srinivasan;T. Nolan;C. Ng
通讯作者：
H. Shear;R. Srinivasan;T. Nolan;C. Ng
影响因子：
32.4
作者：
TIVOL, EA;BORRIELLO, F;SHARPE, AH
通讯作者：
SHARPE, AH
影响因子：
32.4
作者：
Perez, VL;VanParijs, L;Abbas, AK
通讯作者：
Abbas, AK
DOI：
10.1073/pnas.95.17.10067
发表时间：
1998-08-18
影响因子：
11.1
作者：
Hurwitz, AA;Yu, TFY;Allison, JP
通讯作者：
Allison, JP
影响因子：
32.4
作者：
Greenwald, RJ;Boussiotis, VA;Sharpe, AH
通讯作者：
Sharpe, AH