NAADP mediated calcium release from acidic stores plays a critical role in downstream physiological responses of naïve CD4 and CD8 T cells (IRM10P.757)

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most potent Ca2+ mobilizing second messenger discovered to date and has been implicated in Ca2+ signaling in human Jurkat lymphoma T cells via ryanodine receptor activation. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells has not been investigated. In the current study, we demonstrated for the first time to our knowledge the importance of NAADP in the generation of Ca2+ signals in murine conventional naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the impact of NAADP on the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological endpoints such as proliferation, cytokine production, and other responses to stimulation of murine naive T cells. Moreover, we demonstrated that acidic stores in addition to the endoplasmic reticulum are the relevant Ca2+ stores that were sensitive to NAADP in naive T cells.