Strack P, Martin C, Saito S, Dekruyff R H, Ju S T
Arthritis Center, Boston University School of Medicine, MA 02118.
Eur J Immunol. 1990 Jan;20(1):179-84. doi: 10.1002/eji.1830200126.
The effect of various metabolic inhibitors on the expression of cytolytic activity of CD4 (TH1) and CD8 (CTL) clones was studied. The cytolytic activity of CD4 clones, but not CD8 clones, was sensitive to the RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide. Conversely, cholera toxin (CT) inhibited cytolytic activity of CD8, but not CD4 clones. Both mitomycin C, a DNA synthesis inhibitor, and cyclosporin A (CsA) failed to inhibit the cytolytic activity of either CD4 or CD8 clones. Although pretreatment with CsA or CT did not inhibit the cytolytic activity of CD4 clones, lymphokine (interleukin 2, IL2, interferon-gamma, IFN-gamma, and tumor necrosis factor, TNF) production was strongly inhibited. Similarly, pretreatment of a CD8 clone with actinomycin D or CsA inhibited lymphokine production without affecting cytolytic activity. The production of mRNA for TNF and IFN-gamma by concanavalin A-activated CD4 clones was also inhibited by CsA and CT. Moreover, perforin-specific mRNA was not detected in activated CD4 clones. Collectively, these observations demonstrated that de novo synthesis of RNA and protein is required for expression of cytolytic activity of CD4 clones, yet production of TNF, INF-gamma, IL 2 and perforin is not involved. In contrast, the cytolytic machinery of CD8 clones is present prior to activation and is quickly expressed following activation even when de novo synthesis of RNA, protein and lymphokines is blocked.
研究了各种代谢抑制剂对CD4（TH1）和CD8（CTL）克隆细胞溶解活性表达的影响。CD4克隆的细胞溶解活性对RNA合成抑制剂放线菌素D和蛋白质合成抑制剂环己酰亚胺敏感，而CD8克隆则不敏感。相反，霍乱毒素（CT）抑制CD8克隆的细胞溶解活性，但不抑制CD4克隆。DNA合成抑制剂丝裂霉素C和环孢素A（CsA）均未能抑制CD4或CD8克隆的细胞溶解活性。虽然用CsA或CT预处理不抑制CD4克隆的细胞溶解活性，但细胞因子（白细胞介素2、IL2、干扰素-γ、IFN-γ和肿瘤坏死因子、TNF）的产生受到强烈抑制。同样，用放线菌素D或CsA预处理CD8克隆可抑制细胞因子产生，而不影响细胞溶解活性。CsA和CT也抑制伴刀豆球蛋白A激活的CD4克隆产生TNF和IFN-γ的mRNA。此外，在激活的CD4克隆中未检测到穿孔素特异性mRNA。总的来说，这些观察结果表明，CD4克隆细胞溶解活性的表达需要RNA和蛋白质的从头合成，但TNF、INF-γ、IL 2和穿孔素的产生与之无关。相反，CD8克隆的细胞溶解机制在激活前就已存在，即使RNA、蛋白质和细胞因子的从头合成被阻断，激活后也能迅速表达。
