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Eur J Immunol. 2015 Jun;45(6):1794-807. doi: 10.1002/eji.201445209. Epub 2015 Apr 27.

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

Author information

1
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
2
Junior Research Group Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.
3
Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.
4
Center for Infectious Medicine, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden.

Abstract

NK cells represent a vital component of the innate immune system. The recent discoveries demonstrating that the functionality of NK cells 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 NK cells needs to be better understood. Our results provide strong evidence for NKT cell-induced effects on key biological features of NK cells. NKT-cell activation results in the generation of highly active CD27(high) NK cells 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 NK cells, crucial players in viral control. Thus, our findings reveal new fundamental aspects of the NKT-NK cell axis that provide important hints for the manipulation of NK cells in clinical settings.

KEYWORDS:

NK-cell differentiation; NK-cell education; NKT cells; mCMV; αGalCerMPEG

PMID:
25808315
DOI:
10.1002/eji.201445209
[Indexed for MEDLINE]
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