Loss of interferon-induced Stat1 phosphorylation in activated T cells.
Loss of interferon-induced Stat1 phosphorylation in activated T cells.
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活化 T 细胞中干扰素诱导的 Stat1 磷酸化丧失。
DOI：
10.1089/jir.2004.24.169
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Teague,TKent
中科院分区：
文献类型：
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作者：
VanDeWiele,CJustin;Marino,JulieH;Whetsell,MichaelE;Vo,StephenS;Masengale,RhondaM;Teague,TKent
T细胞活化后细胞因子反应性的调节是决定T细胞与抗原相遇后命运的重要机制。我们用超抗原激活小鼠体内的T细胞，并评估它们在干扰素-γ(IFN-γ)和IFN-α的作用下磷酸化Stat1的能力。在体内激活4小时后，T细胞对任一细胞因子的磷酸化Stat1能力不足。IFN敏感性的丧失伴随着细胞因子信号（SOCS）基因（SOCS1、SOCS3和SOCS7）多种抑制因子mRNA转录的增加。这些SOCS的转录水平仅在激活后的最初几个小时内升高，并在60小时内处于或低于正常水平。同样，激活诱导的IFN-α信号抑制是短暂的，激活后3天恢复敏感性。然而，对IFN-γ敏感性的丧失持续存在，并且在第3天仍然明显。这些数据表明，特异性抑制IFN-γ信号的soc独立机制可能存在于T细胞应答的后期阶段。Stat1信号的缺失可能是T细胞在激活过程中和激活后分化的一个因素，也可能是免疫应答过程中对抗IFN-γ毒性作用的一种保护机制。
Modulation of cytokine responsiveness following T cell activation represents an important mechanism that shapes the fate of T cells after encounters with antigens. We activated T cells in mice with superantigen and assessed their ability to phosphorylate Stat1 in response to interferon-γ(IFN-γ) and IFN-α. After 4 h of activationin vivo, T cells became deficient in their ability to phosphorylate Stat1 in response to either cytokine. The loss of IFN sensitivity was accompanied by increased mRNA transcription for multiple suppressors of cytokine signaling (SOCS) genes (SOCS1, SOCS3, and SOCS7). The transcript levels of these SOCS were elevated only during the early hours after activation and were at or below normal levels by 60 h. Likewise, the activation-induced inhibition of IFN-αsignaling was transient, and sensitivity was restored by 3 days postactivation. The loss of sensitivity to IFN-γpersisted, however, and was still evident at 3 days. These data suggest that SOCS-independent mechanisms specific for inhibition of IFN-γsignaling may be present at later stages of the T cell response. The loss of Stat1 signaling may be a factor in differentiation of T cells during and after activation, and it could also represent a protective mechanism against the toxic effects of IFN-γduring immune responses.