Ebert E C
Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Gastroenterology. 1998 Dec;115(6):1439-45. doi: 10.1016/s0016-5085(98)70022-8.
BACKGROUND & AIMS: This study examined the effects of interleukin (IL)-15 on intraepithelial lymphocytes (IELs) because they resemble memory cells that react to IL-15 and are located next to epithelial cells that produce IL-15.
Proliferative responses were measured by [3H]thymidine uptake; interferon (IFN)-gamma production by enzyme-linked immunosorbent assay; and cytotoxicity production by lysis of 51Cr-labeled HT-29 cells.
The proliferative response of IELs was much greater with IL-15 than with equivalent amounts of IL-2 or IL-7 (P < 0.001); the same level of blastogenesis was induced by 10(3)-fold less IL-15 than IL-2. Production of IFN-gamma was also highest when IELs were stimulated with IL-15. IELs lysed more 51Cr-labeled HT-29 cells when cultured for 72 hours with IL-15 (48% +/- 3% at 25:1 effector-to-target ratio) than with IL-2 (27% +/- 3%) or IL-7 (12% +/- 2%) (P < 0.0001). Similarly, limiting dilution analysis revealed a greater frequency of cytotoxic precursors in IELs that were stimulated by IL-15 rather than IL-2: 1/467 vs. 1/1900. But IL-15 did not alter the number of natural killer cells, as determined by quantitating CD16 and CD56 by immunofluorescence. Rather, it increased serine esterase content in IELs.
IL-15 is the most potent of the known cytokines for IELs, inducing the highest levels of proliferation, IFN-gamma production, and cytotoxicity.
本研究检测了白细胞介素（IL）-15对上皮内淋巴细胞（IEL）的影响，因为IEL类似于可对IL-15产生反应的记忆细胞，且位于产生IL-15的上皮细胞旁。
通过[3H]胸腺嘧啶核苷摄取测定增殖反应；采用酶联免疫吸附测定法检测干扰素（IFN）-γ的产生；通过51Cr标记的HT-29细胞裂解检测细胞毒性的产生。
与等量的IL-2或IL-7相比，IL-15刺激下IEL的增殖反应要强得多（P<0.001）；诱导相同水平的细胞分裂所需的IL-15量比IL-2少1000倍。用IL-15刺激IEL时，IFN-γ的产生也最高。与IL-2（27%±3%）或IL-7（12%±2%）相比，IEL与IL-15培养72小时后裂解的51Cr标记的HT-29细胞更多（效应细胞与靶细胞比例为25:1时为48%±3%）（P<0.0001）。同样，有限稀释分析显示，IL-15刺激的IEL中细胞毒性前体的频率高于IL-2刺激的IEL：1/467对1/1900。但通过免疫荧光定量CD16和CD56测定，IL-15并未改变自然杀伤细胞的数量。相反，它增加了IEL中丝氨酸酯酶的含量。
IL-15是已知细胞因子中对IEL作用最强的，可诱导最高水平的增殖、IFN-γ产生和细胞毒性。
