Demirci Gulcin, Li Xian Chang
Department of Medicine, Harvard Medical School, Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Cell Mol Immunol. 2004 Apr;1(2):123-8.
It has been shown that IL-2 and IL-15 can have opposing effects on life and death of T cells. However, the role of IL-2 and IL-15 in regulating the fate of other cell types is less clear. In the present study, we examined the impact of IL-2 and IL-15 on life and death of pre-B cells using the BAF-B03 line. We showed that BAF-B03 cells constitutively expressed the private IL-2R alpha chain and IL-15R alpha chain, and the shared IL-2R beta chain and gamma c chain. Stimulation of BAF-B03 cells in vitro with IL-2 and IL-15 induced vigorous cell proliferation in a dose-dependent fashion. Titration of IL-2 and IL-15 in the assay showed that the mitotic effects of IL-2 and IL-15 were remarkably similar. However, the sensitivities of BAF-B03 cells to Fas mediated apoptosis after IL-2 and IL-15 stimulation were strikingly different. Cells cultured in IL-2 readily underwent apoptotic cell death upon cross-linking of the Fas receptor whereas cells cultured in IL-15 were extremely resistant to Fas triggered cell death. The anti-apoptotic effect of IL-15 in this model was associated with increased expression of Bcl-xL. FLIP expression, however, was comparable between IL-2 and IL-15 stimulated cells. We conclude that IL-2 and IL-15 have diametrically opposite effect on the fate of BAF-B03 cells, although both cytokines share similar receptor structure and exhibit similar mitotic activities.
已有研究表明，白细胞介素 -2（IL -2）和白细胞介素 -15（IL -15）对T细胞的生死可能具有相反的作用。然而，IL -2和IL -15在调节其他细胞类型命运中的作用尚不清楚。在本研究中，我们使用BAF - B03细胞系研究了IL -2和IL -15对前B细胞生死的影响。我们发现BAF - B03细胞组成性表达特异性的IL -2Rα链和IL -15Rα链，以及共同的IL -2Rβ链和γc链。体外使用IL -2和IL -15刺激BAF - B03细胞会以剂量依赖的方式诱导强烈的细胞增殖。在实验中对IL -2和IL -15进行滴定表明，IL -2和IL -15的促有丝分裂作用非常相似。然而，IL -2和IL -15刺激后，BAF - B03细胞对Fas介导的凋亡的敏感性却显著不同。在IL -2中培养的细胞在Fas受体交联后容易发生凋亡性细胞死亡，而在IL -15中培养的细胞对Fas触发的细胞死亡具有极强的抗性。在该模型中，IL -15的抗凋亡作用与Bcl - xL表达增加有关。然而，在IL -2和IL -15刺激的细胞之间，FLIP表达相当。我们得出结论，尽管两种细胞因子具有相似的受体结构并表现出相似的有丝分裂活性，但IL -2和IL -15对BAF - B03细胞的命运具有完全相反的作用。
