Wingett D G, Forcier K, Nielson C P
Department of Veterans Affairs Medical Center, Boise, Idaho 83702, USA.
Cell Immunol. 1999 Mar 15;192(2):203-12. doi: 10.1006/cimm.1998.1440.
CD40L expression is well recognized to be of critical importance in initiation of the immune response. Because cAMP mediates actions of bronchodilators commonly used in asthma, the effects of cAMP in regulating the immune response are of major importance. Cyclic AMP was found to either inhibit or markedly increase CD40L expression dependent upon the mechanisms of T cell activation. Cyclic AMP inhibited CD40L expression induced by TCR activation. In contrast, cAMP enhanced CD40L induced by CD2-mediated T cell activation or by calcium-dependent mechanisms. While neither CD28 costimulation nor exogenous IL-2 or IL-4 prevented cAMP inhibition in TCR activated cells, addition of calcium ionophore to TCR activation prevented any inhibitory effects and caused cAMP to increase CD40L expression. Actions of cAMP to increase CD40L expression appeared independent of PKC and were not a reflection of generalized cellular activation since neither CD25 nor CD69 expression was affected. The markedly contrasting actions of cAMP to decrease or increase CD40L expression, an important control point in the immune response, could be relevant to actions of commonly used medications including bronchodilators.
CD40L表达在免疫反应启动中具有至关重要的作用，这一点已得到广泛认可。由于环磷酸腺苷（cAMP）介导哮喘常用支气管扩张剂的作用，因此cAMP在调节免疫反应中的作用至关重要。研究发现，cAMP根据T细胞激活机制的不同，对CD40L表达产生抑制或显著增加的作用。cAMP抑制TCR激活诱导的CD40L表达。相反，cAMP增强由CD2介导的T细胞激活或钙依赖机制诱导的CD40L表达。虽然CD28共刺激以及外源性白细胞介素-2（IL-2）或白细胞介素-4（IL-4）均不能阻止TCR激活细胞中cAMP介导的抑制作用，但在TCR激活时添加钙离子载体可消除任何抑制作用，并使cAMP增加CD40L表达。cAMP增加CD40L表达的作用似乎独立于蛋白激酶C（PKC），且并非普遍细胞激活的反映，因为CD25和CD69的表达均未受影响。cAMP对免疫反应中重要控制点CD40L表达产生的显著相反作用，可能与包括支气管扩张剂在内的常用药物的作用相关。
