Bodor J, Spetz A L, Strominger J L, Habener J F
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Boston, MA 02114, USA.
Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3536-41. doi: 10.1073/pnas.93.8.3536.
Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells. The ability of T cells to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature peripheral T lymphocytes. Here we show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER (inducible cAMP early repressor) previously described in the hypothalamic-pituitary-gonadal axis. Further, in transcriptional assays in vivo, ICER inhibits calcineurin-mediated expression of the interleukin 2 promoter as well as Tax-mediated transactivation of the human T-lymphotropic virus type I (HTLV-I) promoter. Thus, the induction of ICER in T cells may play an important role in the cAMP-induced quiescence and the persistent latency of HTLV-I.
环磷酸腺苷（cAMP）依赖性信号通路的激活对T细胞的增殖和效应功能具有抑制作用。T细胞在人类胸腺发育过程中获得了在细胞内形成高浓度cAMP的能力，并且大多数成熟外周T淋巴细胞都保留了这种能力。我们在此表明，T细胞中升高的cAMP水平与先前在下丘脑 - 垂体 - 性腺轴中描述的强效转录抑制因子ICER（诱导型cAMP早期抑制因子）的表达相关。此外，在体内转录试验中，ICER抑制钙调神经磷酸酶介导的白细胞介素2启动子的表达以及Tax介导的I型人类嗜T淋巴细胞病毒（HTLV - I）启动子的反式激活。因此，T细胞中ICER的诱导可能在cAMP诱导的静止状态以及HTLV - I的持续潜伏中起重要作用。
