Ly49C impairs NK cell memory in mouse cytomegalovirus infection

Catherine Forbes, Tony Scalzo, Mariapia Degli-Esposti, Jerome Coudert

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3 Citations (Scopus)

Abstract

© Copyright 2016 by The American Association of Immunologists, Inc. All rights reserved.NK cells possess inhibitory receptors that are responsible for self-MHC class I recognition; beyond their inhibitory function, accumulating evidence indicates that such receptors confer NK cell functional competence through an unclear process termed "licensing." Ly49C is the main self-specific inhibitory Ly49 receptor in H-2b C57BL/6 (B6) mice. We used B6 Ly49C-transgenic and B6 b2 microglobulin (b2m)-knockout Ly49C-transgenic mice to investigate the impact of licensing through this inhibitory receptor in precursor and mature NK cells. We found that self-specific inhibitory receptors affected NK cell precursor survival and proliferation at particular developmental stages in an MHC class I-dependent manner. The presence of Ly49C impacted the NK cell repertoire in a b2m-dependent manner, with reduced Ly49A+, Ly49G2+, and Ly49D+ subsets, an increased DNAM-1+ subset, and higher NKG2D expression. Licensed NK cells displayed a skewed distribution of the maturation stages, which was characterized by differential CD27 and CD11b expression, toward the mature phenotypes. We found that Ly49C-mediated licensing induced a split effect on NK cell functions, with increased cytokine-production capabilities following engagement of various activating receptors while cytotoxicity remained unchanged. Analysis of licensed NK cell functions in vivo, in a system of mouse CMV infection, indicated that licensing did not play a major role in the NK cell antiviral response during acute infection, but it strongly impaired the generation and/or persistence of memory NK cells. This study unravels multifaceted effects of licensing on NK cell populations and their functions.
Original languageEnglish
Pages (from-to)128-140
JournalJournal of Immunology
Volume197
Issue number1
DOIs
Publication statusPublished - 2016

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    Forbes, C., Scalzo, T., Degli-Esposti, M., & Coudert, J. (2016). Ly49C impairs NK cell memory in mouse cytomegalovirus infection. Journal of Immunology, 197(1), 128-140. https://doi.org/10.4049/jimmunol.1600199