Thymocytes between the β-selection and positive selection checkpoints are nonresponsive to IL-7 as assessed by STAT-5 phosphorylation
Thymocytes between the β-selection and positive selection checkpoints are nonresponsive to IL-7 as assessed by STAT-5 phosphorylation
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DOI：
10.4049/jimmunol.172.7.4235
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Teague, TK
中科院分区：
文献类型：
--
作者：
Van de Wiele, CJV;Marino, JH;Teague, TK
Interleukin-7 被广泛认为是参与 T 细胞发育的主要稳态因子。为了评估参与选择过程的胸腺细胞的 IL-7 反应性，我们使用一种新的基于流式细胞术的灵敏测定法来检测特定小鼠胸腺细胞亚群中由 IL-7 诱导的 STAT-5 的细胞内磷酸化。使用这种方法，我们发现最早的胸腺细胞亚群（CD4（-）CD8（-）CD25（-）CD44（+））包含IL-7反应细胞和非反应细胞。下一发育阶段（CD4（-）CD8（-）CD25（+）CD44（+）（和-））的过渡与这些群体中所有胸腺细胞的反应性相关。胸腺细胞通过β选择的传代导致IL-7敏感性显着降低。在发育的下一阶段（TCR-和TCR(low)CD69(-)），胸腺细胞对IL-7的作用完全不敏感。然而，在参与正选择过程的胸腺细胞（TCR（低）CD69（+）和TCR中）中再次观察到响应IL-7的STAT-5磷酸化。正如预期的那样，CD4 和 CD8 单阳性胸腺细胞对 IL-7 有反应。这些发现描绘了β选择和正选择检查点之间的IL-7不敏感群体，其中包括预计由于正选择失败而被忽视而死亡的胸腺细胞。这种敏感性模式表明了一种双信号机制，通过该机制控制胸腺细胞在这些检查点的存活。
Interleukin-7 is widely accepted as a major homeostatic factor involved in T cell development. To assess the IL-7 responsiveness of thymocytes involved in selection processes, we used a new sensitive flow cytometry-based assay to detect intracellular phosphorylation of STAT-5 induced by IL-7 in defined mouse thymocyte subsets. Using this method, we found the earliest thymocyte subset (CD4(-)CD8(-)CD25(-)CD44(+)) to contain both IL-7-responsive and nonresponsive cells. Transition through the next stages of development (CD4(-)CD8(-)CD25(+)CD44(+) (and -)) was associated with responsiveness of all thymocytes within these populations. Passage of thymocytes through beta-selection resulted in a significant reduction in IL-7 sensitivity. In the next phases of development (TCR- and TCR(low)CD69(-)), thymocytes were completely insensitive to the effects of IL-7. STAT-5 phosphorylation in response to IL-7 was again observed, however, in thymocytes involved in the positive selection process (TCR(low)CD69(+) and TCRintermediate). As expected, CD4 and CD8 single-positive thymocytes were responsive to IL-7. These findings delineate an IL-7-insensitive population between the beta-selection and positive selection checkpoints encompassing thymocytes predicted to die by neglect due to failure of positive selection. This pattern of sensitivity suggests a two-signal mechanism by which survival of thymocytes at these checkpoints is governed.