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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
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, Volume 9, No. 7, Article e101224, Year 2014
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Description
Background: 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. © 2014 Jenum et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4081517/bin/pone.0101224.s001.eps
Authors & Co-Authors
Jenum, Synne
Norway, Oslo
Oslo Universitetssykehus
Grewal, Harleen M.S.
Norway, Bergen
Universitetet I Bergen
Norway, Bergen
Haukeland Universitetssjukehus
Hokey, David A.
United States, Rockville
Aeras
Kenneth, John
India, Bengaluru
St. John's Research Institute
Vaz, Mario
India, Bengaluru
St. John's Medical College
Doherty, Timothy Mark
Denmark, Brondby
Glaxosmithkline Denmark A/s
Jahnsen, Frode L.
Norway, Oslo
Oslo Universitetssykehus
Doherty, T. M.
Denmark, Copenhagen
Glaxo-smithkline
Lindtjörn, Bernt
Norway, Bergen
Universitetet I Bergen
Hesseling, Anneke Catharina
South Africa, Cape Town
Desmond Tutu tb Centre
Jacob, Auburn J.W.
India
Emmaus Swiss Leprosy Project
Jahnsen, F. L.
Norway, Oslo
Rikshospitalet-radiumhospitalet hf
Kurpad, Anura Vishwanath
India, Bengaluru
St. John's Research Institute
MacAden, Ragini S.
India, Bengaluru
St. John's Research Institute
Nelson, Jesuraj
India, Bengaluru
St. John's Research Institute
Sumithra, Selvam
India, Bengaluru
St. John's Research Institute
Vaz, Manjulika
India, Bengaluru
St. John's Research Institute
Cárdenas, Vicky
United States, Rockville
Aeras
Statistics
Citations: 18
Authors: 18
Affiliations: 11
Identifiers
Doi:
10.1371/journal.pone.0101224
e-ISSN:
19326203
Research Areas
Infectious Diseases
Study Design
Cohort Study
Study Approach
Qualitative