Luyendyk James, Olivas O Renee, Ginger Lisa A, Avery Anne C
Department of Pharmacology and Toxicology, Institute for Environmental Toxicology, National Food Safety and Toxicology Center, Michigan State University, East Lansing, Michigan 48824, USA.
Infect Immun. 2002 Jun;70(6):2941-9. doi: 10.1128/IAI.70.6.2941-2949.2002.
Antigen-presenting cells (APC) play a key role in orchestrating immune responses. T-cell proliferative responses are inhibited during the erythrocyte stages of malaria infection, and a number of studies have suggested that APC are responsible for this phenomenon. In the present studies we examine individual components of the T-cell-activating function of APC: expression of costimulatory and major histocompatibility complex (MHC) class II proteins, the ability to process and present antigen to T cells, and the ability to support cytokine production. We find that during the acute phases of Plasmodium yoelii erythrocyte stage infection, APC upregulate the expression of class II MHC and CD80, maintain expression of CD86, process and present antigen, and support gamma interferon production. However the CD11b(+) subpopulation produces a soluble factor or factors that specifically inhibit interleukin-2 (IL-2) production by responding CD4 T cells. This factor is distinct from prostaglandin E(2), NO, or transforming growth factor beta. The data suggest that IL-2 suppression observed during malaria infection is not due to functional defects of APC but is triggered by production of a factor(s) that actively suppresses production of IL-2 by T cells.
抗原呈递细胞（APC）在协调免疫反应中起关键作用。在疟疾感染的红细胞阶段，T细胞增殖反应受到抑制，多项研究表明APC是造成这一现象的原因。在本研究中，我们检测了APC激活T细胞功能的各个组成部分：共刺激分子和主要组织相容性复合体（MHC）II类蛋白的表达、处理和呈递抗原给T细胞的能力以及支持细胞因子产生的能力。我们发现，在约氏疟原虫红细胞阶段感染的急性期，APC上调II类MHC和CD80的表达，维持CD86的表达，处理和呈递抗原，并支持γ干扰素的产生。然而，CD11b(+)亚群产生一种可溶性因子或多种因子，特异性抑制反应性CD4 T细胞产生白细胞介素-2（IL-2）。该因子不同于前列腺素E2、一氧化氮或转化生长因子β。数据表明，疟疾感染期间观察到的IL-2抑制并非由于APC的功能缺陷，而是由一种或多种因子的产生触发，这些因子积极抑制T细胞产生IL-2。
