烟酸腺嘌呤二核苷酸磷酸(NAADP),被确定为最有效的钙动员第二信使之一,已经在不同的真核细胞类型中进行了研究,包括淋巴细胞。尽管淋巴细胞中NAADP介导的钙释放方面仍在争论中,与NAADP介导的钙释放有关的细胞器通常被表征为酸性并且与溶酶体有关。虽然NAADP介导的钙释放在不同的T细胞亚群,包括天真,效应和天然调节性T细胞,已经研究过了,它在记忆CD4+T细胞中尚未被广泛研究,显示不同的钙通量曲线。使用药理学方法,NAADP途径拮抗剂Ned-19的作用,NAADP参与小鼠记忆性CD4+T细胞的TCR激活及其下游效应子功能,如增殖和细胞因子的产生,被研究过。根据这项研究,Ned-19抑制TCR介导的钙通量及其在原代记忆CD4+T细胞中的下游效应子功能。该研究还揭示了细胞外和细胞内钙的储存,包括内质网和溶酶体样酸性钙储存,有助于TCR介导的记忆CD4+T细胞的钙通量。NAADP-AM,NAADP的细胞通透性类似物,显示在记忆CD4T细胞中释放钙,并且Ned-19抑制钙通量。
Nicotinic acid adenine dinucleotide phosphate (
NAADP), identified as one of the most potent calcium-mobilizing second messengers, has been studied in different eukaryotic cell types, including lymphocytes. Although aspects of
NAADP-mediated calcium release in lymphocytes are still under debate, the organelles pertaining to
NAADP-mediated calcium release are often characterized as acidic and related to lysosomes. Although
NAADP-mediated calcium release in different subsets of T cells, including naïve, effector and natural regulatory T cells, has been studied, it has not been widely studied in memory CD4+ T cells, which show a different calcium flux profile. Using a pharmacological approach, the effect of Ned-19, an NAADP pathway antagonist, on the involvement of NAADP in TCR activation in murine memory CD4+ T cells and their downstream effector functions, such as proliferation and cytokine production, was studied. According to this study, Ned-19 inhibited TCR-mediated calcium flux and its downstream effector functions in primary memory CD4+ T cells. The study also revealed that both extracellular and intracellular calcium stores, including endoplasmic reticulum and lysosome-like acidic calcium stores, contribute to the TCR-mediated calcium flux in memory CD4+ T cells.
NAADP-AM, a cell permeable analogue of
NAADP, was shown to release calcium in memory CD4+ T cells and calcium flux was inhibited by Ned-19.