Cutting edge: Bcl-3 up-regulation by signal 3 cytokine (IL-12) prolongs survival of antigen-activated CD8 T cells
Cutting edge: Bcl-3 up-regulation by signal 3 cytokine (IL-12) prolongs survival of antigen-activated CD8 T cells
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DOI：
10.4049/jimmunol.174.2.600
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发表时间：
2005-01-15
影响因子：
4.4
通讯作者：
Mescher, MF
中科院分区：
文献类型：
--
作者：
Valenzuela, JO;Hammerbeck, CD;Mescher, MF
T细胞的克隆扩增需要在反应的增殖阶段期间的细胞分裂和存活。幼稚的鼠CD 8 T细胞对抗原和共刺激的反应经历了一个流产的反应，其特征是克隆扩增受损，未能发展效应功能，和长期耐受性。由IL-12提供的第三个信号是完全扩展、激活和建立记忆所必需的。由IL-12支持的增强的存活和因此的克隆扩增不是由于Bcl-2或Bcl-x（L）表达增加;两者都被信号1和2最大程度地激活。相比之下，Bcl-3最近显示出当在T细胞中异位表达时增强存活，仅当IL-12存在时增加。此外，对Bcl-3缺陷型CD 8 T细胞的检查表明，IL-12引起的存活率增加依赖于Bcl-3。表达的时间过程表明，Bcl-2和Bcl-xL促进生存早期的反应，而Bcl-3的行为在反应后期。
Clonal expansion of T cells requires cell division and survival during the proliferative phase of the response. Naive murine CD8 T cells responding to Ag and costimulation undergo an abortive response characterized by impaired clonal expansion, failure to develop effector functions, and long-term tolerance. A third signal provided by IL-12 is required for full expansion, activation, and establishment of memory. The enhanced survival, and thus clonal expansion, supported by IL-12 is not due to increased Bcl-2 or Bcl-x(L) expression; both are maximally activated by signals 1 and 2. In contrast, Bcl-3 recently shown to enhance survival when ectopically expressed in T cells, is increased only when IL-12 is present. Furthermore, examination of Bcl-3-deficient CD8 T cells demonstrates that the increased survival caused by IL-12 depends upon Bcl-3. The time courses of expression suggest that Bcl-2 and Bcl-xL promote survival early in the response, whereas Bcl-3 acts later in the response.