Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death.
Signals through 4-1BB are costimulatory to previously activated splenic T cells and inhibit activation-induced cell death.
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DOI：
10.4049/jimmunol.158.6.2600
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发表时间：
1997-03
影响因子：
4.4
通讯作者：
J. Hurtado;Y. J. Kim;B. Kwon
中科院分区：
文献类型：
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作者：
J. Hurtado;Y. J. Kim;B. Kwon
以前，我们和其他人表明，通过小鼠T细胞Ag 4-1BB传递的信号增强了初级T细胞反应，并且阻断4-1BB与其配体的相互作用导致对多克隆活化剂和同种异体抗原的反应降低。由于4-1BB表达是在初级刺激后诱导的，因此我们研究了通过该分子的信号传导在增殖T细胞再激活中的作用。为此，预活化的，4- 1BB-表达T细胞的存在下，板固定的单克隆抗体直接针对4-1BB或原型共刺激分子CD 28的再刺激。在这项工作中，我们表明，在任何一种信号的存在下，T细胞响应TCR交联与强烈的增殖反应和细胞因子的产生;此外，我们的研究结果表明，T细胞增殖部分与表面4-1BB表达相关。此外，我们的研究结果表明，抗体介导的共刺激信号可以独立于潜在的辅助B7-CD 28/CTLA-4（细胞毒性T淋巴细胞Ag-4）的相互作用。重要的是，在TCR重新接合后观察到的特征性DNA片段化和凋亡性细胞死亡在4-1BB或CD 28信号传导的存在下被抑制。
Previously, we and others showed that signals relayed through the murine T cell Ag 4-1BB enhance primary T cell responses, and that blocking the interaction of 4-1BB with its ligand results in decreased responses to polyclonal activators and to alloantigens. Because 4-1BB expression is induced following primary stimulation, we investigated the role of signaling through this molecule in the reactivation of proliferating T cells. To this end, preactivated, 4-1BB-expressing T cells were restimulated in the presence of plate-immobilized mAbs directed against 4-1BB or the prototypic costimulatory molecule CD28. In this work, we show that in the presence of either signal, T cells respond to TCR cross-linking with strong proliferative responses and cytokine production; moreover, our findings indicate that T cell proliferation partially correlates with surface 4-1BB expression. In addition, our results suggest that Ab-mediated costimulatory signals can act independently of potential accessory B7-CD28/CTLA-4 (cytotoxic T lymphocyte Ag-4) interactions. Importantly, the characteristic DNA fragmentation and apoptotic cell death observed after TCR re-engagement are inhibited comparably in the presence of either 4-1BB or CD28 signaling.