Cellular and molecular regulation of vaccination with heat shock protein 60 from Histoplasma capsulatum
Cellular and molecular regulation of vaccination with heat shock protein 60 from Histoplasma capsulatum
复制标题
DOI：
10.1128/iai.70.7.3759-3767.2002
复制
发表时间：
2002-07-01
影响因子：
3.1
通讯作者：
Gibbons, RS
中科院分区：
文献类型：
--
作者：
Deepe, GS;Gibbons, RS
接种来自荚膜组织胞浆菌的热休克蛋白 60 (Hsp60) 疫苗可诱导小鼠产生保护性免疫反应。我们探索了重组 Hsp60 在小鼠中发挥功效的细胞和分子要求。根据存活率以及肺和脾脏中的真菌负荷评估，在疫苗接种诱导阶段，CD4（+）细胞而非CD8（+）细胞的耗尽消除了保护作用。在表达阶段，免疫后消除CD4(+)或CD8(+)细胞并不会显着改变真菌从致死攻击中恢复或存活的情况。 Hsp60 疫苗接种后两个亚群的耗竭导致无法控制致命感染以及肺和脾脏中更高的真菌负担。接种 Hsp60 的小鼠脾细胞释放的细胞因子比接种荚膜梭菌重组 Hsp70 或牛血清白蛋白的小鼠细胞产生更多的 γ 干扰素和白细胞介素 10 和 -12。 γ干扰素（而非白细胞介素10）的产生依赖于T细胞，特别是CD4(+)细胞。在疫苗接种诱导期用抗γ干扰素或白细胞介素-10或-12的单克隆抗体治疗Hsp60免疫小鼠，伴随着来自肺和脾的酵母细胞回收率的增加以及100%的死亡率。同样，γ干扰素或白细胞介素12的中和消除了表达期Hsp60的保护作用。这些结果描绘了针对这种真菌的疫苗接种所需的调控元件的复杂性。
Vaccination with heat shock protein 60 (Hsp60) from Histoplasma capsulatum induces a protective immune response in mice. We explored the cellular and molecular requirements for the efficacy of recombinant Hsp60 in mice. Depletion of CD4(+), but not CD8(+), cells during the inductive phase of vaccination abolished protection, as assessed by survival and by the fungal burden in lungs and spleens. In the expressive phase, the elimination of CD4(+) or CD8(+) cells after immunization did not significantly alter fungal recovery or survival from a lethal challenge. Depletion of both subpopulations after Hsp60 vaccination resulted in a failure to control a lethal infection and a higher fungal burden in lungs and spleens. Cytokine release by spleen cells from mice vaccinated with Hsp60 produced substantially more gamma interferon and interleukin-10 and -12 than that of cells from mice immunized with either H. capsulatum recombinant Hsp70 or bovine serum albumin. The generation of gamma interferon, but not of interleukin-10, was dependent on T cells, in particular CD4(+) cells. Treatment of Hsp60-immunized mice with monoclonal antibody to gamma interferon or interleukin-10 or -12 in the inductive phase of vaccination was accompanied by increased recovery of yeast cells from lungs and spleens and 100% mortality. Likewise, the neutralization of gamma interferon or interleukin-12 abolished the protective effect of Hsp60 in the expressive phase. These results delineate the complexity of the regulatory elements necessary for vaccination against this fungus.