Bulfone-Paus S, Ungureanu D, Pohl T, Lindner G, Paus R, Rückert R, Krause H, Kunzendorf U
Institute of Immunology, Benjamin Franklin Medical Center, Free University Berlin, Germany.
Nat Med. 1997 Oct;3(10):1124-8. doi: 10.1038/nm1097-1124.
Interleukin-15 shares many biological activities with IL-2 and signals through the IL-2 receptor beta and gamma chains. However, IL-15 and IL-2 differ in their controls of expression and secretion, their range of target cells and their functional activities. These dissimilarities may include differential effects on apoptosis. For example, IL-2 induces or inhibits T-cell apoptosis in vitro, depending on T-cell activation, whereas IL-15 inhibits cytokine deprivation-induced apoptosis in activated T cells. Studying whether and how IL-15 modulates distinct apoptosis pathways, we show here that apoptosis induced by anti-Fas, anti-CD3, dexamethasone, and/or anti-IgM in activated human T and B cells in vitro is inhibited by IL-15 in a manner dependent on RNA synthesis. In vivo, anti-Fas-induced lethal multisystem apoptosis in mice is suppressed by a novel IL-15-IgG2b fusion protein. Only IL-15, but not IL-2, completely protected from lethal hepatic failure. Thus, IL-15 is a potent, general inhibitor of apoptosis in vitro and in vivo with intriguing therapeutic potential.
白细胞介素-15与白细胞介素-2具有许多生物学活性，并通过白细胞介素-2受体β链和γ链进行信号传导。然而，白细胞介素-15和白细胞介素-2在表达和分泌的调控、靶细胞范围及其功能活性方面存在差异。这些差异可能包括对细胞凋亡的不同影响。例如，白细胞介素-2在体外诱导或抑制T细胞凋亡，这取决于T细胞的激活状态，而白细胞介素-15则抑制激活的T细胞中细胞因子剥夺诱导的凋亡。在研究白细胞介素-15是否以及如何调节不同的凋亡途径时，我们在此表明，白细胞介素-15以依赖于RNA合成的方式抑制体外激活的人T细胞和B细胞中由抗Fas、抗CD3、地塞米松和/或抗IgM诱导的凋亡。在体内，新型白细胞介素-15-IgG2b融合蛋白可抑制小鼠中抗Fas诱导的致死性多系统凋亡。只有白细胞介素-15，而不是白细胞介素-2，能完全预防致死性肝衰竭。因此，白细胞介素-15在体外和体内都是一种有效的、通用的细胞凋亡抑制剂，具有引人注目的治疗潜力。
