Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, Brazil.
Microbes Infect. 2013 Mar;15(3):181-91. doi: 10.1016/j.micinf.2012.11.007. Epub 2012 Nov 28.
Paracoccidioidomycosis is a granulomatous systemic mycosis endemic in Brazil and other Latin America countries. A DNA vaccine encoding the immunoprotective peptide 10 (P10) significantly reduced the fungal burden in mice when given prior to or after intratracheal challenge with Paracoccidioides brasiliensis. Presently, the generation/expansion of CD4+ CD44hi memory T cells as well as Foxp3+ Treg cells in mice immunized with the DNA vaccine (pcDNA3-P10) before and after infection with P. brasiliensis was investigated. Memory CD4+ CD44hi T cells simultaneously with Foxp3+ Treg cells increased in the spleens and lungs of pcDNA3-P10 immunized mice on day 0, 30, 60 and 120 postinfection. Histopathology of the lung tissue showed minimal inflammation in immunized mice compared with the unimmunized group, suggesting a role for regulatory T cells in controlling the immunopathology. The DNA vaccine shows that the repeated immunization generates memory cells and regulatory T cells that replace the initially protective pro-inflammatory T cells conferring a long term protection while preserving the integrity of the infected tissue.
球孢子菌病是一种在巴西和其他拉丁美洲国家流行的肉芽肿性系统性真菌病。在经气管内接种巴西球孢子菌之前或之后给予编码免疫保护肽 10（P10）的 DNA 疫苗，可显著降低小鼠中的真菌负担。目前，研究了在感染巴西球孢子菌之前和之后用 DNA 疫苗（pcDNA3-P10）免疫的小鼠中 CD4+ CD44hi 记忆 T 细胞和 Foxp3+ Treg 细胞的产生/扩增。在感染后第 0、30、60 和 120 天，pcDNA3-P10 免疫小鼠的脾脏和肺部中同时增加了记忆性 CD4+ CD44hi T 细胞和 Foxp3+ Treg 细胞。与未免疫组相比，免疫小鼠的肺组织病理学显示炎症最小，提示调节性 T 细胞在控制免疫病理学中发挥作用。该 DNA 疫苗表明，重复免疫可产生记忆细胞和调节性 T 细胞，这些细胞取代最初具有保护作用的促炎 T 细胞，从而提供长期保护，同时保持受感染组织的完整性。
