Department of Microbiology, University of Iowa, Iowa City, Iowa, USA.
Nat Immunol. 2011 Dec 11;13(2):188-95. doi: 10.1038/ni.2180.
Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control.
疟原虫感染红细胞会引发临床疟疾。疟原虫特异性 CD4(+) T 细胞与较低的寄生虫载量和人类疟疾的严重程度相关，是控制小鼠血液阶段感染所必需的。然而，决定保护或寄生虫持续存在的 CD4(+) T 细胞特征仍然未知。本文中，作者表明，感染疟原虫会导致与 T 细胞功能障碍相关的抑制性受体 PD-1 表达升高。在体内阻断 PD-1 配体 PD-L1 和抑制性受体 LAG-3 可恢复 CD4(+) T 细胞功能，扩增滤泡辅助 T 细胞和生发中心 B 细胞和浆母细胞的数量，增强保护性抗体，并迅速清除小鼠的血液阶段疟疾。因此，慢性疟疾会导致特定的 T 细胞功能障碍，通过抑制性治疗恢复适当的功能可以增强寄生虫的控制。
