NK cell-like behavior of Valpha14i NK T cells during MCMV infection.

Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Valpha14 invariant natural ki...

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Main Authors: Johnna D Wesley, Marlowe S Tessmer, Deanna Chaukos, Laurent Brossay
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-07-01
Series:PLoS Pathogens
Online Access:https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000106&type=printable
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author Johnna D Wesley
Marlowe S Tessmer
Deanna Chaukos
Laurent Brossay
author_facet Johnna D Wesley
Marlowe S Tessmer
Deanna Chaukos
Laurent Brossay
author_sort Johnna D Wesley
collection DOAJ
description Immunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Valpha14 invariant natural killer T cell response to MCMV has not been examined. We found that Valpha14i NK T cells become activated and produce significant levels of IFN-gamma, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Valpha14i NK T cells into MCMV-infected CD1d(-/-) mice demonstrate that CD1d is dispensable for Valpha14i NK T cell activation. In contrast, both IFN-alpha/beta and IL-12 are required for optimal activation. Valpha14i NK T cell-derived IFN-gamma is partially dependent on IFN-alpha/beta but highly dependent on IL-12. Valpha14i NK T cells contribute to the immune response to MCMV and amplify NK cell-derived IFN-gamma. Importantly, mortality is increased in CD1d(-/-) mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Valpha14i NK T cells that act as effector T cells during bacterial infection, but have NK cell-like behavior during the innate immune response to MCMV infection.
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spelling doaj-art-cf0c8f4b9ceb4e539891e22eb9329a322025-08-20T02:17:29ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742008-07-0147e100010610.1371/journal.ppat.1000106NK cell-like behavior of Valpha14i NK T cells during MCMV infection.Johnna D WesleyMarlowe S TessmerDeanna ChaukosLaurent BrossayImmunity to the murine cytomegalovirus (MCMV) is critically dependent on the innate response for initial containment of viral replication, resolution of active infection, and proper induction of the adaptive phase of the anti-viral response. In contrast to NK cells, the Valpha14 invariant natural killer T cell response to MCMV has not been examined. We found that Valpha14i NK T cells become activated and produce significant levels of IFN-gamma, but do not proliferate or produce IL-4 following MCMV infection. In vivo treatment with an anti-CD1d mAb and adoptive transfer of Valpha14i NK T cells into MCMV-infected CD1d(-/-) mice demonstrate that CD1d is dispensable for Valpha14i NK T cell activation. In contrast, both IFN-alpha/beta and IL-12 are required for optimal activation. Valpha14i NK T cell-derived IFN-gamma is partially dependent on IFN-alpha/beta but highly dependent on IL-12. Valpha14i NK T cells contribute to the immune response to MCMV and amplify NK cell-derived IFN-gamma. Importantly, mortality is increased in CD1d(-/-) mice in response to high dose MCMV infection when compared to heterozygote littermate controls. Collectively, these findings illustrate the plasticity of Valpha14i NK T cells that act as effector T cells during bacterial infection, but have NK cell-like behavior during the innate immune response to MCMV infection.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000106&type=printable
spellingShingle Johnna D Wesley
Marlowe S Tessmer
Deanna Chaukos
Laurent Brossay
NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
PLoS Pathogens
title NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
title_full NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
title_fullStr NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
title_full_unstemmed NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
title_short NK cell-like behavior of Valpha14i NK T cells during MCMV infection.
title_sort nk cell like behavior of valpha14i nk t cells during mcmv infection
url https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000106&type=printable
work_keys_str_mv AT johnnadwesley nkcelllikebehaviorofvalpha14inktcellsduringmcmvinfection
AT marlowestessmer nkcelllikebehaviorofvalpha14inktcellsduringmcmvinfection
AT deannachaukos nkcelllikebehaviorofvalpha14inktcellsduringmcmvinfection
AT laurentbrossay nkcelllikebehaviorofvalpha14inktcellsduringmcmvinfection