约氏疟原虫感染早期CD4^+ CD25^+ Foxp^(3+)调节性T细胞的作用

The role of CD4^+ CD25^+ Foxp^(3+) regulatory T cells in early Plasmodium yoelii 17XL infection

目的探讨调节性T细胞(Tregs)在致死型约氏疟原虫(Plasmodiumyoelii17XL,P.y17XL)感染早期的作用。方法用P.y17XL感染DBA/2、BALB/c及BALB/c Treg消除小鼠,计数红细胞感染率;感染后第0、3和5 d制备脾细胞悬液,ELISA检测脾细胞培养上清中IFN-γ和IL-10水平。结果P.y17XL感染DBA/2和BALB/c小鼠后,其感染结局分别为自愈和死亡。易感BALB/c小鼠于感染前1 d和感染后1 d经CD25单抗处理后,与正常感染小鼠相比原虫血症水平明显降低,生存率提高;脾细胞培养上清中IL-10水平于感染后第3～5 d显著降低,IFN-γ水平于感染后第3d显著增高。结论P.y17XL感染早期,BALB/c小鼠Tregs数量的过早升高影响宿主的易感性。Tregs可能通过分泌细胞因子IL-10抑制Th1型细胞免疫应答的有效建立。

Objective To investigate the role of regulation T cells（Tregs） in early Plasmodium yoelii 17XL（P.y17XL） infection.Methods DBA/2 mice with normal Tregs,BALB/c mice with normal Tregs,and CD25-depleted BALB/c mice were infected by intraperitoneal injection with 1×106 virulent P.y17XL parasitized erythrocytes,and the ratio of infected RBCs was counted.On days 0,3,and 5 post-infection（pi）,splenocyte IFN-γ and IL-10 were dynamically detected by ELISA.Results In DBA/2 and BALB/c mice infected with P.y17XL,infection resulted in spontaneous recovery or death. Tregs were depleted by injection of anti-CD25 mAb in susceptible BALB/c mice infected with P. y17XL. In vivo depletion of Tregs significantly decreased the level of parasitemia and a substantial prolongation of survival time was seen in BALB/c mice. Meanwhile, the level of IL-10 decreased significantly on day 3-5 pi, and that of IFN- γclearly increased on day 3 pi in CD25-depleted BALB/c mice in comparison to BALB/e with normal Tregs. Conclusion Results indicated that the increase in Tregs in BALB/e mice infected with P. y17XL was closely correlated with the susceptibility of the host in the early stages of infection. Tregs inhibited the effective establishment of a Thl immune response in early P. y17XL infection in BALB/c mice. The mechanism regulating this may depend upon IL-10.