Elevated interleukin‐9 receptor expression and response to interleukins‐9 and ‐7 in thymocytes during radiation‐induced T‐cell lymphomagenesis in B6C3F1 mice
Elevated interleukin‐9 receptor expression and response to interleukins‐9 and ‐7 in thymocytes during radiation‐induced T‐cell lymphomagenesis in B6C3F1 mice
复制标题
DOI：
10.1002/jcp.10390
复制
发表时间：
2004-01
影响因子：
5.6
通讯作者：
M. Nishimura;S. Kakinuma;D. Yamamoto;Yoshiro Kobayashi;G. Suzuki;T. Sado;Y. Shimada
中科院分区：
文献类型：
--
作者：
M. Nishimura;S. Kakinuma;D. Yamamoto;Yoshiro Kobayashi;G. Suzuki;T. Sado;Y. Shimada
在白血病发生的早期和晚期，细胞因子受体表达和细胞因子反应的失调在肿瘤前细胞的发育和扩张或肿瘤细胞的进展中起着重要的作用。为了确定在放射诱导的淋巴瘤发生的早期阶段，起始细胞中赋予显著生长的关键变化，我们在分剂量照射后的B6C3F1小鼠中检测了胸腺源性细胞因子受体的表达和胸腺细胞对细胞因子的反应，在T细胞淋巴瘤发生之前。照射后，胸腺T细胞亚群经历了由受体表达决定的两个阶段的延迟再生。第一阶段发生在辐照后1周内，并伴有强烈表达IL - 1、IL - 2、IL - 6、IL - 7、IL - 15和tnf - α受体基因的T细胞亚群的短暂扩增。第二阶段发生在照射后12周，以IL - 9Rα表达增加为特征。未辐照对照小鼠胸腺细胞对IL - 9无反应。然而，IL - 9与IL - 7和PHA协同作用，在辐照后的第二个阶段刺激辐照细胞的增殖。此外，与年龄匹配的未辐照对照胸腺细胞相比，这些细胞对IL - 7或PHA单独表现出高反应性。这些结果表明，IL - 9受体的异常表达和/或胸腺细胞对细胞因子的反应性增加是辐射诱导T细胞淋巴瘤发展的关键过程。j .细胞。中国生物医学工程学报，2004,31(2):389 - 391。©2003 Wiley‐Liss, Inc。
Dysregulation of cytokine receptor expression and responsiveness to cytokines is hypothesized to play an important role in the development and expansion of preneoplastic cells or progression of neoplastic cells during the early and late stages of leukemogenesis. To determine the crucial changes in initiated cells that confer significant growth during the early stage of radiation‐induced lymphomagenesis, we examined both the expression of receptors for thymus‐derived cytokines and thymocyte response to cytokines before the onset of T cell lymphomas in B6C3F1 mice after split‐dose irradiation. After irradiation, thymic T cell subsets underwent delayed regeneration consisting of two phases as determined by receptor expression. The first phase occurred within 1 week post‐irradiation and was accompanied by transient expansion of T cell subsets strongly expressing receptor genes for IL‐1, IL‐2, IL‐6, IL‐7, IL‐15, and TNFα. The second phase occurred 12 weeks after irradiation and was characterized by increased expression of IL‐9Rα. Thymocytes from non‐irradiated control mice were unresponsive to IL‐9. However, IL‐9 acted synergistically with IL‐7 and PHA to stimulate the proliferation of irradiated cells during the second post‐irradiation phase. Moreover, these cells showed hyper‐responsiveness to IL‐7 or PHA alone compared to age‐matched non‐irradiated control thymocytes. These results suggest that the unusual expression of IL‐9 receptors and/or increased responsiveness of thymocytes to cytokines are key processes in the development of radiation‐induced T cell lymphomas. J. Cell. Physiol. 198: 82–90, 2004. © 2003 Wiley‐Liss, Inc.