cAMP差异调控CD39+、CTLA-4+、PD-1+T细胞亚群产生OA北大核心CSTPCD

Objective:To analyze expression and models of CD39,CTLA-4,and PD-1 on T cells,to investigate effect of cyclic adenosine monophosphate(cAMP)on their expressions,and to analyze key pathways regulating their expressions.Methods:Small molecules such as adenylate cyclase(ACs)activators,phosphodiesterase(PDE)inhibitors,protein kinase A(PKA)inhibitors and PKA-CREB inhibitors were used to stimulate rhesus macaque peripheral blood mononuclear cells in vitro,and changes in ratios of CD39,CTLA-4,and PD-1 positive(CD39+,CTLA-4+,and PD-1+)T cells were detected by flow cytometry,and to analyze their expression patterns,and effects of small molecules on ratio of positively expressing/co-expressing cells were compared to clarify expres-sion patterns and molecules and pathways that regulated expression.Results:Normal macaque CD4+T and CD8+T cells had low ratios of CD39+,CTLA-4+,and PD-1+cells,and positive cells predominantly expressed only one of these molecules.Increasing intracellular cAMP levels did not affect CD39+T cell ratio,significantly increased CTLA-4+T cell ratio,and decreased PD-1+CD8+T cell ratio,involving cell populations with mono expression of CTLA-4 and PD-1.Inhibition of PKA activity reduced potentiation of CTLA-4 expression by broad-spectrum PDE inhibitor,3-isobutyl-1-methylxanthine(IBMX),but did not affect PD-1 expression.Exchange protein activated by cAMP did not affect CTLA-4 expression but downregulate PD-1+CD4+/CD8+T cells ratio.Upregulation of CTLA-4 by PDE4B selective inhibitors was similar to IBMX,while regulation of PDE3 and PDE5A selective inhibitors on PD-1 expression was similar to IBMX.Conclusion:CD39,CTLA-4 and PD-1 have different expression models on T cells but are differentially regulated by cAMP levels and have different cAMP downstream signal pathways involved in expression regulation.