Activated NKT cells imprint NK-cell differentiation, functionality and education.

Abstract

NKcells represent a vital component of the innate immune system. The recent discoveries demonstrating that the functionality of NKcells depends on their differentiation and education status underscore their potential as targets for immune intervention. However, to exploit their full potential, a detailed understanding of the cellular interactions involved in these processes is required. In this regard, the cross-talk between NKT cells and NKcells needs to be better understood. Our results provide strong evidence for NKT cell-induced effects on key biological features of NKcells. NKT-cell activation results in the generation of highly active CD27(high) NKcells with improved functionality. In this context, degranulation activity and IFNγ production were mainly detected in the educated subset. In a mCMV infection model, we also demonstrated that NKT-cell stimulation induced the generation of highly functional educated and uneducated NKcells, crucial players in viral control. Thus, our findings reveal new fundamental aspects of the NKT-NKcell axis that provide important hints for the manipulation of NKcells in clinical settings.