Churilla A M, Braciale V L
J Immunol. 1987 Mar 1;138(5):1338-45.
In this study, we examine the expression of IL 2 receptors on class I and class II MHC-restricted, influenza-specific murine T lymphocyte clones at early (day 3) and late (day 8 to day 12) times after antigenic stimulation. IL 2 receptor expression on the three clones examined increases to peak levels early and subsequently decays 10-fold to 50-fold during this time period, as evidenced by monoclonal anti-IL 2 receptor antibody binding. However, in IL 2 binding site studies these clones retain high levels of high-affinity IL 2 receptors (46 to 97% of day 3 levels) at the later time points, despite their inability to proliferate in response to IL 2 in the form of supernatant from Con A-stimulated rat splenocytes. Considerable clone to clone variation is seen in binding site affinity for IL 2, whereas no significant change in binding affinity for IL 2 is exhibited for a particular clone as a function of time after activation, suggesting little structural change in the IL 2 receptor with time. Contrary to this finding, Con A-stimulated murine splenocytes exhibit a sharp decay in IL 2 receptor expression reaching 25% of peak (day 3) levels by day 10 after stimulation by lectin, with a significant decrease in the average binding site affinity for IL 2 in the population. This change in affinity in the Con A-stimulated population may, however, reflect a selection with time for lymphocytes with lower affinity for IL 2. To elucidate where the potential block may be that prevents these CTL clones from proliferating in an IL 2-dependent manner, the ability of the cells to internalize bound IL 2 at late times after activation is examined. All three clones late after activation are able to internalize bound IL 2 with efficiencies equivalent to that seen at day 3. Additionally, two of the three clones late after activation are able to upregulate expression of IL 2 receptors in response to picamolar concentrations of IL 2, indicating that the receptors on these clones are able to transmit a signal, although insufficient to induce proliferation of the cells. These observations strongly suggest that for the CTL clones examined, at late times after antigenic stimulation, engagement of IL 2 by the high-affinity receptor is not a sufficient signal to induce cells to transit through the cell cycle.
在本研究中，我们检测了I类和II类主要组织相容性复合体（MHC）限制的、流感特异性小鼠T淋巴细胞克隆在抗原刺激后早期（第3天）和晚期（第8天至第12天）白细胞介素2（IL 2）受体的表达情况。通过单克隆抗IL 2受体抗体结合证明，所检测的三个克隆上的IL 2受体表达在早期增加至峰值水平，随后在此时间段内下降10倍至50倍。然而，在IL 2结合位点研究中，尽管这些克隆无法对来自刀豆蛋白A（Con A）刺激的大鼠脾细胞的上清液形式的IL 2作出增殖反应，但在较晚时间点它们仍保留高水平的高亲和力IL 2受体（为第3天水平的46%至97%）。在IL 2结合位点亲和力方面，克隆间存在相当大的差异，而对于特定克隆，其对IL 2的结合亲和力在激活后的时间内未表现出显著变化，这表明IL 2受体的结构随时间变化很小。与这一发现相反，Con A刺激的小鼠脾细胞在凝集素刺激后第10天，IL 2受体表达急剧下降，达到峰值（第3天）水平的25%，群体中对IL 2的平均结合位点亲和力显著降低。然而，Con A刺激群体中这种亲和力的变化可能反映了随着时间推移对IL 2亲和力较低的淋巴细胞的选择。为了阐明潜在的阻断可能发生在哪里，从而阻止这些细胞毒性T淋巴细胞（CTL）克隆以依赖IL 2的方式增殖，我们检测了激活后较晚时间细胞内化结合的IL 2的能力。所有三个克隆在激活后较晚时间都能够内化结合的IL 2，效率与第3天所见相当。此外，三个克隆中有两个在激活后较晚时间能够响应皮摩尔浓度的IL 2上调IL 2受体的表达，这表明这些克隆上的受体能够传递信号，尽管不足以诱导细胞增殖。这些观察结果强烈表明，对于所检测的CTL克隆，在抗原刺激后的较晚时间，高亲和力受体与IL 2的结合不是诱导细胞通过细胞周期的充分信号。
