Novak T J, Rothenberg E V
Division of Biology, California Institute of Technology, Pasadena 91125.
Proc Natl Acad Sci U S A. 1990 Dec;87(23):9353-7. doi: 10.1073/pnas.87.23.9353.
In this report, we explore the nature of the inductive stimuli leading to expression of the divergently regulated lymphokines interleukin 2 (IL-2) and interleukin 4 (IL-4). Elevation of cAMP levels blocks IL-2 induction while sparing IL-4 induction. These effects are gene-specific, not cell-specific, and can be observed in the same cells. Transient transfection experiments using murine IL-2 regulatory sequences to drive expression of a reporter gene show at least part of the inhibition to act at the transcriptional level. The possible biological significance of these results is indicated by the observation that representative type 2 helper T-cell lines maintain significantly higher levels of cAMP per cell than a type 1 helper T-cell line. Fresh splenic CD4+ T cells, which preferentially make IL-2, have particularly low levels of cAMP per cell and a low capacity to elevate cAMP in response to forskolin. However, their response to forskolin increases significantly after several days of stimulation. These results suggest a potential link between differential cAMP regulation and the divergence of memory T cells into effector subsets.
在本报告中，我们探究了导致差异性调控的淋巴因子白细胞介素2（IL-2）和白细胞介素4（IL-4）表达的诱导刺激的本质。环磷酸腺苷（cAMP）水平的升高会阻断IL-2的诱导，而不影响IL-4的诱导。这些效应是基因特异性的，而非细胞特异性的，并且可以在同一细胞中观察到。使用小鼠IL-2调控序列驱动报告基因表达的瞬时转染实验表明，至少部分抑制作用发生在转录水平。有代表性的2型辅助性T细胞系每个细胞维持的cAMP水平显著高于1型辅助性T细胞系，这一观察结果表明了这些结果可能具有的生物学意义。新鲜的脾脏CD4+ T细胞优先产生IL-2，每个细胞的cAMP水平特别低，并且对福斯高林升高cAMP的能力也较低。然而，在刺激数天后，它们对福斯高林的反应显著增加。这些结果表明，cAMP差异调节与记忆T细胞分化为效应子亚群之间存在潜在联系。
