Kuiper H M, de Jong R, Brouwer M, Lammers K, Wijdenes J, van Lier R A
Central Laboratory, Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Immunology. 1994 Sep;83(1):38-44.
Interaction of CD28 with its ligand B7 plays an important role in the initiation of immune responses. The co-stimulatory signal generated by cross-linking of CD28 molecules results in enhanced T-cell proliferation and augmentation of cytokine production. In particular, mRNA levels of T-helper 1 (Th1)-type cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) are reported to be strongly increased. We investigated the effect of CD28 co-stimulation on the production of Th2-type cytokines. CD28 mAb induced a strong augmentation of IL-2 secretion in activated T-cell clones. Production of IFN-gamma was also enhanced, but the increase in IL-4 secretion was generally moderate. Augmentation of IL-4 production by CD28 was most pronounced in clones that produced low amounts of IL-2, compared to clones producing high levels of IL-2. It was found that the up-regulation of IL-4 by CD28 co-stimulation was mainly controlled indirectly via an increase of IL-2. Some clones could produce IL-4 in an IL-2-independent manner; in these situations CD28 co-stimulation had no augmenting effect on the production of IL-4. The secretion of IL-4 by peripheral blood CD4+ T cells, that were activated with B7-expressing transfectants, was also found to be dependent on IL-2. Finally, Northern blot analysis confirmed that co-stimulation of CD28 primarily affected IL-2 production, and that inhibition of IL-2/IL-2 receptor interaction abolished the augmenting action of CD28 monoclonal antibody on the production of the Th2-type cytokines IL-4, IL-5 and IL-10 and of the Th1 cytokine IFN-gamma.
CD28与其配体B7的相互作用在免疫反应的启动中起重要作用。CD28分子交联产生的共刺激信号导致T细胞增殖增强和细胞因子产生增加。特别是，据报道辅助性T细胞1（Th1）型细胞因子如白细胞介素-2（IL-2）和干扰素-γ（IFN-γ）的mRNA水平显著增加。我们研究了CD28共刺激对Th2型细胞因子产生的影响。CD28单克隆抗体在活化的T细胞克隆中诱导IL-2分泌强烈增加。IFN-γ的产生也增强，但IL-4分泌的增加通常较为适度。与产生高水平IL-2的克隆相比，CD28对IL-4产生的增强在产生低水平IL-2的克隆中最为明显。发现CD28共刺激对IL-4的上调主要通过IL-2的增加间接控制。一些克隆可以以不依赖IL-2的方式产生IL-4；在这些情况下，CD28共刺激对IL-4的产生没有增强作用。用表达B7的转染子激活的外周血CD4 + T细胞分泌IL-4也被发现依赖于IL-2。最后，Northern印迹分析证实CD28的共刺激主要影响IL-2的产生，并且抑制IL-2 / IL-2受体相互作用消除了CD28单克隆抗体对Th2型细胞因子IL-4、IL-5和IL-10以及Th1细胞因子IFN-γ产生的增强作用。
