Taylor-Robinson A W, Phillips R S
Division of Infection and Immunity, University of Glasgow, UK.
Scand J Immunol. 1998 Nov;48(5):527-34. doi: 10.1046/j.1365-3083.1998.00437.x.
Plasmodium chabaudi infection of mice provides an excellent model for examining acquired immunity to the blood-borne stage of malaria infection. CD4+ T-cell receptor (TCR) alphabeta-bearing T lymphocytes play a critical role in mediating protection, ascribed to both T helper (Th) 1 and Th2 subsets. One factor that may influence the Th1/Th2 cell balance is infective dose. In this study, we found that the size of the infective dose of P. chabaudi, and thus the level of antigen presented to the immune system, correlated with the balance of responder CD4+ T-cell phenotypes. Increasing the infective dose in a resistant mouse strain enhanced the Th1 cytokine (interferon-gamma; IFN-gamma) response and reduced the Th2 cytokine (interleukin-4; IL-4) response. In contrast, increasing the infective dose in a susceptible mouse strain led to a prominent and accelerated up-regulation of IL-4 production. These data show that the dose of antigen can significantly affect the balance between Th1- and Th2-mediated immune functions during infection of the mammalian host with blood-stage malaria parasites. This demonstration that parasite numbers may modulate CD4+ T-cell regulation has novel implications for the successful implementation of antimalarial vaccination and chemotherapeutic strategies.
小鼠感染查巴迪疟原虫为研究针对疟疾感染血源阶段的获得性免疫提供了一个极佳的模型。携带αβ型CD4⁺T细胞受体（TCR）的T淋巴细胞在介导保护作用中发挥关键作用，这归因于辅助性T细胞（Th）1和Th2亚群。可能影响Th1/Th2细胞平衡的一个因素是感染剂量。在本研究中，我们发现查巴迪疟原虫感染剂量的大小，以及因此呈现给免疫系统的抗原水平，与应答性CD4⁺T细胞表型的平衡相关。在抗性小鼠品系中增加感染剂量会增强Th1细胞因子（干扰素-γ；IFN-γ）反应并降低Th2细胞因子（白细胞介素-4；IL-4）反应。相反，在易感小鼠品系中增加感染剂量会导致IL-4产生显著且加速上调。这些数据表明，在哺乳动物宿主感染血期疟原虫期间，抗原剂量可显著影响Th1和Th2介导的免疫功能之间的平衡。这一寄生虫数量可能调节CD4⁺T细胞调节的证明，对抗疟疫苗接种和化疗策略的成功实施具有新的意义。
