Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role ofNAADPin Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using theNAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells.
Bibliographical noteFunding Information:
This work was supported by a University of Toledo Interdisciplinary Research Initiation Program Grant and National Institutes of Health Grants GM100444 (to J. S.) and DE023418 (to D. G.). This work was taken in part from the doctoral dissertation submitted by R. A. A. to the University of Toledo College of Graduate Studies for the Ph.D. degree in Medicinal Chemistry, December 2014. The authors declare that they have no conflicts of interest with the contents of this article