Delayed and Separate Costimulation In Vitro Supports the Evidence of a Transient “Excited” State of CD8+ T Cells During Activation
Delayed and Separate Costimulation In Vitro Supports the Evidence of a Transient “Excited” State of CD8+ T Cells During Activation
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DOI：
10.4049/jimmunol.164.9.4493
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发表时间：
2000-05
期刊：
影响因子：
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通讯作者：
N. Pardigon;C. Cambouris;N. Bercovici;F. Lemaître;R. Liblau;P. Kourilsky
中科院分区：
文献类型：
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作者：
N. Pardigon;C. Cambouris;N. Bercovici;F. Lemaître;R. Liblau;P. Kourilsky
尽管T细胞激活的双信号模型表明，最佳刺激需要通过TCR的信号1和共刺激信号2，但现在很清楚，在某些条件下可以绕过共刺激的要求。我们之前报道过，这是体外初始CD8+ T细胞的情况。在本研究中，我们测试了信号1被破坏后信号2传递的效果。采用固定化重组单链MHC分子作为信号1，体外刺激TCR转基因小鼠的幼稚CD8+ T细胞。然后在不同的时间长度后停止该信号，并立即或在一段时间后给予抗cd28单抗作为信号2。我们发现，当信号2按顺序相加时，可以增强短信号1。此外，两个信号之间的时间差并不能消除这种增强作用。如果增加信号1的强度，而不增加其持续时间，则可以延长信号1和信号2传递之间的时间差，而不会失去增强。总之，我们的研究结果表明，这两个信号不需要同时传递就能获得最佳的T细胞激活。我们认为CD8+ T细胞在单独受到信号1刺激后可以达到短暂的“兴奋”状态，其特征是细胞能够对分离的和延迟的信号2做出反应。
Although the two-signal model for T cell activation states that a signal-1 through the TCR and a costimulatory signal-2 are required for optimal stimulation, it is now clear that the requirement for costimulation can be bypassed under certain conditions. We previously reported that this is the case for naive CD8+ T cells in vitro. In the present study we tested the effect of signal-2 when delivered after signal-1 has been disrupted. Naive CD8+ T cells from TCR transgenic mice were stimulated in vitro by using immobilized recombinant single-chain MHC molecules alone as signal-1. This signal was then stopped after different lengths of time, and anti-CD28 mAb as signal-2 was given either immediately or after a time lag. We found that signal-2 can potentiate a short signal-1 when added sequentially. Moreover, a time lag between the two signals does not abolish this potentiation. If the strength of signal-1, but not its duration, is increased, then the time lag between the delivery of signals 1 and 2 can be lengthen without loss of potentiation. Together, our results indicate that the two signals do not need to be delivered concomitantly to get optimal T cell activation. We suggest that the CD8+ T cells can reach a transient “excited” state after being stimulated with signal-1 alone, characterized by the cell’s ability to respond to separate and delayed signal-2.