Distinct APC subtypes drive spatially segregated CD4+ and CD8+ T-Cell effector activity during skin infection with HSV-1

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dc.contributor.authorMacleod, Bethany L
dc.contributor.authorBedoui, Sammy
dc.contributor.authorHor, Jyh Liang
dc.contributor.authorMueller, Scott N
dc.contributor.authorRussell, Tiffany A
dc.contributor.authorHollett, Natasha A
dc.contributor.authorHeath, William R
dc.contributor.authorTscharke, David C
dc.contributor.authorBrooks, Andrew G
dc.contributor.authorGebhardt, Thomas
dc.date.accessioned2015-03-05T00:20:00Z
dc.date.available2015-03-05T00:20:00Z
dc.date.issued2014-08-14
dc.date.updated2016-06-14T08:57:01Z
dc.description.abstractEfficient infection control requires potent T-cell responses at sites of pathogen replication. However, the regulation of T-cell effector function in situ remains poorly understood. Here, we show key differences in the regulation of effector activity between CD4+ and CD8+ T-cells during skin infection with HSV-1. IFN-γ-producing CD4+ T cells disseminated widely throughout the skin and draining lymph nodes (LN), clearly exceeding the epithelial distribution of infectious virus. By contrast, IFN-γ-producing CD8+ T cells were only found within the infected epidermal layer of the skin and associated hair follicles. Mechanistically, while various subsets of lymphoid- and skin-derived dendritic cells (DC) elicited IFN-γ production by CD4+ T cells, CD8+ T cells responded exclusively to infected epidermal cells directly presenting viral antigen. Notably, uninfected cross-presenting DCs from both skin and LNs failed to trigger IFN-γ production by CD8+ T-cells. Thus, we describe a previously unappreciated complexity in the regulation of CD4+ and CD8+ T-cell effector activity that is subset-specific, microanatomically distinct and involves largely non-overlapping types of antigen-presenting cells (APC).
dc.description.sponsorshipThe work was funded by grant (APP628423 and APP1059514) and fellowship support from the National Health and Medical Research Council Australia (NHMRC)and the Australian Research Council (ARC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_AU
dc.format15 pages
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/1885/12809
dc.publisherPublic Library of Science
dc.relationhttp://purl.org/au-research/grants/nhmrc/628423
dc.relationhttp://purl.org/au-research/grants/nhmrc/1059514
dc.relationhttp://purl.org/au-research/grants/arc/ft110100310
dc.relationhttp://purl.org/au-research/grants/nhmrc/1005846
dc.rights© 2014 Macleod et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.sourcePLoS Pathogens
dc.subjectHSV infection
dc.subjectPeripheral infection
dc.subjectT-cell immunity
dc.subjectT-cell effector function
dc.titleDistinct APC subtypes drive spatially segregated CD4+ and CD8+ T-Cell effector activity during skin infection with HSV-1
dc.typeJournal article
dcterms.dateAccepted2014-06-25
local.bibliographicCitation.issue8en_AU
local.bibliographicCitation.lastpage15
local.bibliographicCitation.startpagee1004303en_AU
local.contributor.affiliationTscharke, David C., Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University Russell, Tiffany A., Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National University Hollett, Natasha A., Division of Biomedical Science and Biochemistry, Research School of Biology, The Australian National Universityen_AU
local.contributor.authoremaildavid.tscharke@anu.edu.auen_AU
local.contributor.authoruidu4334102en_AU
local.identifier.absfor060506 - Virology
local.identifier.absseo920109 - Infectious Diseases
local.identifier.ariespublicationu4008405xPUB41
local.identifier.citationvolume10en_AU
local.identifier.doi10.1371/journal.ppat.1004303en_AU
local.identifier.essn1553-7374en_AU
local.identifier.scopusID2-s2.0-84953344184
local.identifier.thomsonID000341576300026
local.identifier.uidSubmittedByu4334102en_AU
local.publisher.urlhttp://www.plos.org/en_AU
local.type.statusPublished Versionen_AU

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