Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation

Abstract

Background: Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD 1 ) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown. Objective: The objective of this study is to further dissect the mechanism of actions of NAD 1 and determine the effect of APCs on NAD 1 -mediated T-cell activation. Methods: Isolated dendritic cells and bone marrow-derived mast cells (MCs) were used to characterize the mechanisms of action of NAD 1 on CD4 1 T-cell fate in vitro. Furthermore, NAD 1 -mediated CD4 1 T-cell differentiation was investigated in vivo by using wild-type C57BL/6, MC 2/2 , MHC class II 2/2 , Wiskott-Aldrich syndrome protein (WASP) 2/2 , 5C.C7 recombination-activating gene 2 (Rag2) 2/2 , and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of NAD 1 on the systemic immune response in the context of Listeria monocytogenes infection.