PROPRIOCIDAL APOPTOSIS OF MATURE T-LYMPHOCYTES OCCURS AT S-PHASE OF THE CELL-CYCLE
PROPRIOCIDAL APOPTOSIS OF MATURE T-LYMPHOCYTES OCCURS AT S-PHASE OF THE CELL-CYCLE
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DOI：
10.1002/eji.1830230724
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发表时间：
1993-07-01
影响因子：
5.4
通讯作者：
LENARDO, MJ
中科院分区：
文献类型：
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作者：
BOEHME, SA;LENARDO, MJ
我们发现，成熟的未转化的CD4+和CD8 + T淋巴细胞可以通过预处理白细胞介素-4（IL-4）或白细胞介素-2（IL-2）对T细胞受体（TcR）介导的凋亡敏感。对死亡的敏感性程度可能与细胞周期水平相关，如通过胸苷掺入、细胞倍增时间或在S期掺入溴脱氧尿苷的细胞数量所测量的。然而，使用药理学细胞周期阻断剂，我们发现，通过细胞周期的进展是不需要细胞死亡。相反，我们发现细胞必须处于细胞周期的某个阶段才能对TcR介导的死亡敏感。阻滞于G1期的细胞对T细胞受体诱导的细胞凋亡具有抵抗性，而阻滞于S期的细胞对T细胞受体诱导的细胞凋亡具有敏感性。这些观察结果表明，生长淋巴因子的一个重要特征是它们能够驱动T细胞进入细胞周期的部分，在那里它们对抗原受体诱导的细胞凋亡敏感。此外，这些结果提供了额外的证据，即T细胞生长淋巴因子IL-2和IL-4可能通过细胞凋亡参与下调T细胞反应-我们称之为“杀propriocidal调节”的途径。
We found that mature nontransformed CD4+ and CD8+ T lymphocytes could be made susceptible to T cell receptor(TcR)-mediated apoptosis by pretreatment with interleukin-4 (IL-4) or interleukin-2 (IL-2). The degree of susceptibility to death could be correlated with the level of cell cycling as measured by thymidine incorporation, cell doubling times, or the number of cells incorporating bromodeoxyuridine during S phase. However, using pharmacologic cell cycle blocking agents,we found that progression through the cell cycle was not required for cell death. Rather, we found that cells must be in a certain phase of the cell cycle to be susceptible to TcR-mediated death. Cells blocked in G1 phase were resistant to T cell receptor-induced apoptosis, whereas cells blocked in S phase were susceptible. These observations suggest that an important feature of growth lymphokines is their ability to drive T cells into portions of the cell cycle where they are sensitive to antigen receptor-induced apoptosis. Furthermore, these results provide additional evidence that the T cell growth lymphokines IL-2 and IL-4 may participate in the down-regulation of T cell responses by apoptosis - a pathway we have termed ''propriocidal regulation''.