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The frequencies of IFNγ+IL2+TNFα+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® Gold In-Tube response in a prospective study of healthy Indian adolescents

dc.contributor.authorJenum, Synneen_ZA
dc.contributor.authorGrewal, Harleen M. S.en_ZA
dc.contributor.authorHokey, David A.en_ZA
dc.contributor.authorKenneth, Johnen_ZA
dc.contributor.authorVaz, Marioen_ZA
dc.contributor.authorDoherty, Timothy Marken_ZA
dc.contributor.authorJahnsen, Frode Larsen_ZA
dc.contributor.authorHesseling, A. C.en_ZA
dc.date.accessioned2016-03-08T09:44:10Z
dc.date.available2016-03-08T09:44:10Z
dc.date.issued2014-07-03
dc.identifier.citationJenum, S. et al. 2014. The frequencies of IFNγ+IL2+TNFα+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® Gold In-Tube response in a prospective study of healthy Indian adolescents. PLoS ONE, 9(7):e101224, doi:10.1371/journal.pone.0101224.en_ZA
dc.identifier.issn1932-6203 (online)
dc.identifier.otherdoi:10.1371/journal.pone.0101224
dc.identifier.urihttp://hdl.handle.net/10019.1/98260
dc.descriptionPlease cite as follows: Jenum, S. et al. 2014. The frequencies of IFNγ+IL2+TNFα+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® Gold In-Tube response in a prospective study of healthy Indian adolescents. PLoS ONE, 9(7):e101224, doi:10.1371/journal.pone.0101224.en_ZA
dc.descriptionThe original publication is available at http://journals.plos.org/plosoneen_ZA
dc.description.abstractBackground: QuantiFERON-TB Gold In-Tube (QFT) is an IFNγ-release assay used in the diagnosis of Mycobacterium tuberculosis (MTB) infection. The risk of TB progression increases with the magnitude of the MTB-specific IFNγ-response. QFT reversion, also associated with low Tuberculin Skin Test responses, may therefore represent a transient immune response with control of M. tuberculosis infection. However, studies at the single cell level have suggested that the quality (polyfunctionality) of the T-cell response is more important than the quantity of cytokines produced. Objective: To explore the quality and/or magnitude of mycobacteria-specific T-cell responses associated with QFT reversion and persistent QFT-positivity. Methods: Multi-color flowcytometry on prospectively collected peripheral blood mononuclear cells was applied to assess mycobacteria-specific T-cell responses in 42 QFT positive Indian adolescents of whom 21 became QFT negative (reverters) within one year. Ten QFT consistent negatives were also included as controls. Results: There was no difference in the qualitative PPD-specific CD4+ T-cell response between QFT consistent positives and reverters. However, compared with QFT consistent positives, reverters displayed lower absolute frequencies of polyfunctional (IFNγ+IL2+TNFα+) CD4+ T-cells at baseline, which were further reduced to the point where they were not different to QFT negative controls one year later. Moreover, absolute frequencies of these cells correlated well with the magnitude of the QFT-response. Conclusion: Whereas specific polyfunctional CD4+ T-cells have been suggested to protect against TB progression, our data do not support that higher relative or absolute frequencies of PPD-specific polyfunctional CD4+ T-cells in peripheral blood can explain the reduced risk of TB progression observed in QFT reverters. On the contrary, absolute frequencies of these cells correlated with the QFT-response, suggesting that this readout reflects antigenic load.en_ZA
dc.description.urihttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101224
dc.format.extent9 pagesen_ZA
dc.language.isoen_ZAen_ZA
dc.publisherPLoSen_ZA
dc.subjectMycobacterium tuberculosisen_ZA
dc.subjectMycobacterium tuberculosis -- Diagnosisen_ZA
dc.titleThe frequencies of IFNγ+IL2+TNFα+ PPD-specific CD4+CD45RO+ T-cells correlate with the magnitude of the QuantiFERON® Gold In-Tube response in a prospective study of healthy Indian adolescentsen_ZA
dc.typeArticleen_ZA
dc.description.versionPublisher's versionen_ZA
dc.rights.holderAuthors retain copyrighten_ZA


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