Lu P, Zhou X, Chen S J, Moorman M, Morris S C, Finkelman F D, Linsley P, Urban J F, Gause W C
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
J Exp Med. 1994 Aug 1;180(2):693-8. doi: 10.1084/jem.180.2.693.
The costimulatory signal provided to T cells through CTLA-4-ligand interactions is required for T cell activation resulting in increased interleukin 2 (IL-2) production in vitro, but its role in the production of IL-4 and other cytokines is unclear and few in vivo studies have been performed to confirm results of in vitro experiments. We have examined the in vivo effects of blocking CTLA-4 ligands on the T helper cell 2 (Th2)-associated mucosal immune response that follows oral infection of mice with the nematode parasite, Heligmosomoides polygyrus. CTLA-4Ig administration inhibited H. polygyrus-induced increases in mesenteric lymph node (MLN) B cell major histocompatibility complex class II expression and size and T cell-derived IL-4 gene expression. In addition, CTLA-4 immunoglobulin (Ig) partially blocked increased IL-3, IL-5, and IL-9 cytokine gene expression in Peyer's patch (PP) and MLN 8 d after primary inoculation of mice with the parasite. Increases in the number of IL-4- but not IL-5-secreting cells were also inhibited by CTLA-4Ig. H. polygyrus-induced elevations in serum IgE levels but not blood eosinophils, were markedly inhibited by CTLA-4Ig. These results suggest that stimulation of CD28 and/or CTLA-4 is required for T cell priming leading to IL-4 cytokine production, B cell activation, and IgE secretion during a Th2-like, mucosal immune response to a nematode parasite.
通过CTLA-4配体相互作用提供给T细胞的共刺激信号是T细胞激活所必需的，这会导致体外白细胞介素2（IL-2）产生增加，但其在IL-4和其他细胞因子产生中的作用尚不清楚，且很少有体内研究来证实体外实验的结果。我们研究了阻断CTLA-4配体对小鼠经线虫寄生虫多房棘球绦虫口服感染后T辅助细胞2（Th2）相关黏膜免疫反应的体内影响。给予CTLA-4Ig可抑制多房棘球绦虫诱导的肠系膜淋巴结（MLN）B细胞主要组织相容性复合体II类表达、大小增加以及T细胞来源的IL-4基因表达。此外，在小鼠初次接种寄生虫8天后，CTLA-4免疫球蛋白（Ig）部分阻断了派尔集合淋巴结（PP）和MLN中IL-3、IL-5和IL-9细胞因子基因表达的增加。CTLA-4Ig还抑制了分泌IL-4而非IL-5的细胞数量增加。CTLA-4Ig显著抑制了多房棘球绦虫诱导的血清IgE水平升高，但对血液嗜酸性粒细胞无影响。这些结果表明，在对线虫寄生虫的Th2样黏膜免疫反应中，T细胞启动导致IL-4细胞因子产生、B细胞激活和IgE分泌需要CD28和/或CTLA-4的刺激。
