Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways

Human plasmacytoid dendritic cells secrete high levels of IFNa and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN g and enhanced cytotoxicity. We show that pDC mediate these process...

Full description

Bibliographic Details
Main Authors: Heather Donaghy, George Rozis, Martin Goodier, Linda Klavinskis, Frances Gotch, Steven Patterson, Adel Benlahrech
Format: Article
Language:English
Published: MDPI AG 2009-01-01
Series:Sensors
Subjects:
Online Access:http://www.mdpi.com/1424-8220/9/1/386/
_version_ 1811303868139569152
author Heather Donaghy
George Rozis
Martin Goodier
Linda Klavinskis
Frances Gotch
Steven Patterson
Adel Benlahrech
author_facet Heather Donaghy
George Rozis
Martin Goodier
Linda Klavinskis
Frances Gotch
Steven Patterson
Adel Benlahrech
author_sort Heather Donaghy
collection DOAJ
description Human plasmacytoid dendritic cells secrete high levels of IFNa and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN g and enhanced cytotoxicity. We show that pDC mediate these processes by different mechanisms, some of which overlap. Human NK cells were analysed after co-culture with immature or CpG-matured blood pDC or with supernatant from these cells. Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC and did not require pDC contact. Up-regulation was due in part to IFNa but also to factors in IFNa negative supernatant from immature DC. HLA-DR expression was independent of secreted molecules but required contact with immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562 targets and expression of CD107a, was mediated by multiple factors including type I IFN, supernatant from immature pDC cultures and contact with immature or mature pDC. These factors act cumulatively to enhance cytotoxcity. Thus different parameters of pDC mediated NK cell activation are regulated by distinct pathways.
first_indexed 2024-04-13T07:55:53Z
format Article
id doaj.art-84869ffc6bd84f3794e13c5897224245
institution Directory Open Access Journal
issn 1424-8220
language English
last_indexed 2024-04-13T07:55:53Z
publishDate 2009-01-01
publisher MDPI AG
record_format Article
series Sensors
spelling doaj.art-84869ffc6bd84f3794e13c58972242452022-12-22T02:55:24ZengMDPI AGSensors1424-82202009-01-019138640310.3390/s90100386Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different PathwaysHeather DonaghyGeorge RozisMartin GoodierLinda KlavinskisFrances GotchSteven PattersonAdel BenlahrechHuman plasmacytoid dendritic cells secrete high levels of IFNa and are thus implicated in the activation of NK cells. Activated NK cells are characterised by the up-regulation of CD69 and MHC class II DR expression, secretion of IFN g and enhanced cytotoxicity. We show that pDC mediate these processes by different mechanisms, some of which overlap. Human NK cells were analysed after co-culture with immature or CpG-matured blood pDC or with supernatant from these cells. Maximal CD69 expression by NK cells was mediated by supernatant from mature pDC and did not require pDC contact. Up-regulation was due in part to IFNa but also to factors in IFNa negative supernatant from immature DC. HLA-DR expression was independent of secreted molecules but required contact with immature or mature DC. Enhanced NK cytotoxicity, measured by killing of K562 targets and expression of CD107a, was mediated by multiple factors including type I IFN, supernatant from immature pDC cultures and contact with immature or mature pDC. These factors act cumulatively to enhance cytotoxcity. Thus different parameters of pDC mediated NK cell activation are regulated by distinct pathways.http://www.mdpi.com/1424-8220/9/1/386/dendritic cellsNK cellscytokinescytotoxicity
spellingShingle Heather Donaghy
George Rozis
Martin Goodier
Linda Klavinskis
Frances Gotch
Steven Patterson
Adel Benlahrech
Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways
Sensors
dendritic cells
NK cells
cytokines
cytotoxicity
title Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways
title_full Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways
title_fullStr Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways
title_full_unstemmed Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways
title_short Human NK Cell Up-regulation of CD69, HLA-DR, Interferon γ Secretion and Cytotoxic Activity by Plasmacytoid Dendritic Cells is Regulated through Overlapping but Different Pathways
title_sort human nk cell up regulation of cd69 hla dr interferon aza³ secretion and cytotoxic activity by plasmacytoid dendritic cells is regulated through overlapping but different pathways
topic dendritic cells
NK cells
cytokines
cytotoxicity
url http://www.mdpi.com/1424-8220/9/1/386/
work_keys_str_mv AT heatherdonaghy humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways
AT georgerozis humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways
AT martingoodier humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways
AT lindaklavinskis humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways
AT francesgotch humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways
AT stevenpatterson humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways
AT adelbenlahrech humannkcellupregulationofcd69hladrinterferonaza3secretionandcytotoxicactivitybyplasmacytoiddendriticcellsisregulatedthroughoverlappingbutdifferentpathways