Troye-Blomberg M, Berzins K, Perlmann P
Department of Immunology, Stockholm University, Sweden.
Crit Rev Immunol. 1994;14(2):131-55. doi: 10.1615/critrevimmunol.v14.i2.20.
Both antibody-dependent and antibody-independent mechanisms are involved in immune protection against the asexual blood stages of the malaria parasite. It is well established that T cells play a crucial role in both induction and maintenance of this immunity. Of the two T-cell subsets (CD4+, CD8+) carrying alpha/beta T-cell receptors, the CD4+ T cells are of major importance for the development of blood stage immunity in both experimental and human malaria. In mice, CD4+ T cells comprise at least two functionally distinct cell types (TH1, TH2), distinguished on the basis of their lymphokine production. The balance between these subsets is critical for the outcome of an infection. In some rodent malarias, TH1 cells producing IFN-gamma and IL-2 are important for controlling infection in its early phases, while TH2 cells, producing i.a. IL-4 and IL-10, together with antibodies, are important for parasite clearance in later phases of infection. Distinct CD4+ T cells of either TH1 or TH2 type also have regulatory functions in human P. falciparum infection. In contrast to the CD4+ T cells, the role of CD8+ T cells in blood stage infection appears to be limited, but suppression of some CD4+ activities has been reported for both experimental and human malaria. As in other infections, peripheral T cells equipped with gamma/delta receptors are strongly upregulated in malaria and also respond to parasite antigens in vitro by proliferation and lymphokine production. However, the importance of the gamma/delta T cells for protection when compared with pathogenesis is presently unclear. Rapid advances made in recent years in the characterization and cloning of plasmodial antigens eliciting immune protection have made it possible to define some of the antigenic structures involved in T-cell immunity. This, together with an improved understanding of cellular mechanisms, provides some basis for the development of modern malaria vaccines.
抗体依赖和抗体非依赖机制均参与针对疟原虫无性血液阶段的免疫保护。众所周知，T细胞在这种免疫的诱导和维持中都起着关键作用。在携带α/β T细胞受体的两种T细胞亚群（CD4 +、CD8 +）中，CD4 + T细胞对于实验性疟疾和人类疟疾中血液阶段免疫的发展至关重要。在小鼠中，CD4 + T细胞至少包括两种功能不同的细胞类型（TH1、TH2），根据它们产生的淋巴因子来区分。这些亚群之间的平衡对于感染的结果至关重要。在一些啮齿动物疟疾中，产生IFN-γ和IL-2的TH1细胞对于在感染早期控制感染很重要，而产生IL-4和IL-10等细胞因子的TH2细胞以及抗体对于感染后期的寄生虫清除很重要。TH1或TH2型的不同CD4 + T细胞在人类恶性疟原虫感染中也具有调节功能。与CD4 + T细胞相比，CD8 + T细胞在血液阶段感染中的作用似乎有限，但在实验性疟疾和人类疟疾中均报道了对某些CD4 +活性的抑制。与其他感染一样，配备γ/δ受体的外周T细胞在疟疾中强烈上调，并且在体外也通过增殖和产生淋巴因子对寄生虫抗原作出反应。然而，与发病机制相比，γ/δ T细胞在保护方面的重要性目前尚不清楚。近年来在引发免疫保护的疟原虫抗原的表征和克隆方面取得的快速进展使得确定一些参与T细胞免疫的抗原结构成为可能。这与对细胞机制的更好理解一起，为现代疟疾疫苗的开发提供了一些基础。
