CD3- and CD28-dependent induction of PDE7 required for T cell activation
CD3- and CD28-dependent induction of PDE7 required for T cell activation
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DOI：
10.1126/science.283.5403.848
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发表时间：
1999-02-05
期刊：
影响因子：
56.9
通讯作者：
Beavo, JA
中科院分区：
文献类型：
--
作者：
Li, LS;Yee, C;Beavo, JA
CD3 和 CD28 受体的共刺激对于 T 细胞激活至关重要。发现腺苷 3',5'-单磷酸 (cAMP) 特异性磷酸二酯酶 7 (PDE7) 的诱导是这种共刺激的结果。 T 细胞中 PDE7 的增加与 cAMP 的减少、白介素 2 表达的增加以及增殖的增加相关。用PDE7反义寡核苷酸选择性降低PDE7表达可抑制T细胞增殖；通过阻断通过 cAMP 依赖性蛋白激酶 (PKA) 运作的 cAMP 信号通路，可以逆转抑制作用。因此，PDE7 诱导和随后的 PKA 活性抑制是 T 细胞激活所必需的，抑制 PDE7 可能是治疗 T 细胞依赖性疾病的一种方法。
Costimulation of both the CD3 and CD28 receptors is essential for T cell activation. Induction of adenosine 3',5'-monophosphate (cAMP)-specific phosphodiesterase-7 (PDE7) was found to be a consequence of such costimulation. Increased PDE7 in T cells correlated with decreased cAMP, increased interleukin-2 expression, and increased proliferation. Selectively reducing PDE7 expression with a PDE7 antisense oligonucleotide inhibited T cell proliferation; inhibition was reversed by blocking the cAMP signaling pathways that operate through cAMP-dependent protein kinase (PKA). Thus, PDE7 induction and consequent suppression of PKA activity is required for T cell activation, and inhibition of PDE7 could be an approach to treating T cell-dependent disorders.