Esser M T, Dinglasan R D, Krishnamurthy B, Gullo C A, Graham M B, Braciale V L
Department of Microbiology and the Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
J Immunol. 1997 Jun 15;158(12):5612-8.
IL-2 is a T cell growth factor that has pleiotropic functions in T cell differentiation, induction of lymphokine-activated killer cells, and regulation of immune responses. In studying TCR triggering of perforin or Fas ligand (FasL)/Fas (CD95 ligand/CD95) cytotoxicity in our influenza-specific T cell clones, we found that IL-2 can also induce FasL/Fas cytotoxicity. IL-2 induces FasL/Fas cytotoxicity in our CD8+ and CD4+ Th1 clones, but not in our CD4+ Th2 clones. IL-2 induction of cytolytic activity occurs when the CD8+ T cells are refractory to IL-2-induced proliferation. This killing is Ag independent, MHC unrestricted, and blocked by Fas.Fc fusion protein. IL-2 induces FasL/Fas cytotoxicity in a dose-dependent manner, but does not induce high levels of FasL expression as detected by flow cytometry. TCR triggered FasL/Fas cytotoxicity is detectable in CD8+ and Th1 clones by 3 h and peaks at 6 h; high levels of killing are maintained for at least 24 h. Similarly, IL-2 induces FasL/Fas killing in CD8+ and Th1 clones within 3 h of stimulation and maintains high levels for at least 24 h. TCR-triggered FasL/Fas killing is inhibited by emetine and cyclosporin A, whereas IL-2-induced FasL/Fas killing is inhibited by emetine, but not by cyclosporin A. These results demonstrate a second mechanism to induce FasL/Fas cytotoxicity in CD8+ and Th1 clones and may explain IL-2 induction of Ag-independent MHC-unrestricted lymphokine-activated killer cell activity.
白细胞介素-2是一种T细胞生长因子，在T细胞分化、诱导淋巴因子激活的杀伤细胞以及调节免疫反应方面具有多效性功能。在研究我们的流感特异性T细胞克隆中T细胞受体触发穿孔素或Fas配体（FasL）/Fas（CD95配体/CD95）细胞毒性时，我们发现白细胞介素-2也能诱导FasL/Fas细胞毒性。白细胞介素-2在我们的CD8⁺和CD4⁺ Th1克隆中诱导FasL/Fas细胞毒性，但在我们的CD4⁺ Th2克隆中则不会。当CD8⁺ T细胞对白细胞介素-2诱导的增殖产生抗性时，白细胞介素-2会诱导溶细胞活性。这种杀伤不依赖抗原，不受主要组织相容性复合体限制，并被Fas.Fc融合蛋白阻断。白细胞介素-2以剂量依赖的方式诱导FasL/Fas细胞毒性，但通过流式细胞术检测未诱导出高水平的FasL表达。在CD8⁺和Th1克隆中，T细胞受体触发的FasL/Fas细胞毒性在3小时时可检测到，并在6小时达到峰值；高水平的杀伤至少维持24小时。同样，白细胞介素-2在刺激后3小时内在CD8⁺和Th1克隆中诱导FasL/Fas杀伤，并至少维持高水平24小时。T细胞受体触发的FasL/Fas杀伤被依米丁和环孢素A抑制，而白细胞介素-2诱导的FasL/Fas杀伤被依米丁抑制，但不被环孢素A抑制。这些结果证明了在CD8⁺和Th1克隆中诱导FasL/Fas细胞毒性的第二种机制，并可能解释白细胞介素-2诱导的不依赖抗原、不受主要组织相容性复合体限制的淋巴因子激活的杀伤细胞活性。
