Immunology and Infection Laboratory, Queensland Institute of Medical Research and The Australian Centre for Vaccine Development, Herston, Brisbane, Queensland, Australia.
PLoS Pathog. 2010 Dec 9;6(12):e1001221. doi: 10.1371/journal.ppat.1001221.
Studies in malaria patients indicate that higher frequencies of peripheral blood CD4(+) Foxp3(+) CD25(+) regulatory T (Treg) cells correlate with increased blood parasitemia. This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection. In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3(+) cells did not improve parasite control or disease outcome. In contrast, elevating frequencies of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete protection against severe disease. This protection was entirely dependent upon Foxp3(+) cells and resulted in lower parasite biomass, impaired antigen-specific CD4(+) T and CD8(+) T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain. Furthermore, Foxp3(+) cell-mediated protection was dependent upon CTLA-4 but not IL-10. These data show that T cell-mediated parasite tissue sequestration can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology.
疟疾患者的研究表明，外周血 CD4(+) Foxp3(+) CD25(+) 调节性 T (Treg) 细胞的频率升高与血液寄生虫载量增加相关。这一观察结果表明，Treg 细胞会损害病原体的清除，因此在感染期间可能对宿主有害。在感染疟原虫伯氏疟原虫 ANKA 的 C57BL/6 小鼠中，耗尽 Foxp3(+)细胞并不能改善寄生虫的控制或疾病结果。相比之下，使用 IL-2/抗 IL-2 复合物在体内升高天然 Treg 细胞的频率会导致对严重疾病的完全保护。这种保护完全依赖于 Foxp3(+)细胞，并导致寄生虫生物量降低、抗原特异性 CD4(+) T 和 CD8(+) T 细胞反应受损，通常会促进该模型中寄生虫组织的隔离，以及常规 T 细胞向大脑的募集减少。此外，Foxp3(+)细胞介导的保护依赖于 CTLA-4 而不是 IL-10。这些数据表明，在疟疾的小鼠模型中，调节性 T 细胞可以减少 T 细胞介导的寄生虫组织隔离，从而限制疟疾引起的免疫病理学。
