Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states.

2.50
Hdl Handle:
http://hdl.handle.net/10033/141115
Title:
Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states.
Authors:
Sester, Urban; Fousse, Mathias; Dirks, Jan; Mack, Ulrich; Prasse, Antje; Singh, Mahavir; Lalvani, Ajit; Sester, Martina
Abstract:
T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.
Affiliation:
Department of Internal Medicine IV, Saarland University, Homburg, Germany.
Citation:
Whole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states. 2011, 6 (3):e17813 PLoS ONE
Journal:
PloS one
Issue Date:
2011
URI:
http://hdl.handle.net/10033/141115
DOI:
10.1371/journal.pone.0017813
PubMed ID:
21423578
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
Publications of Dept. Gene Regulation and Differentiation (RDIF)

Full metadata record

DC FieldValue Language
dc.contributor.authorSester, Urbanen
dc.contributor.authorFousse, Mathiasen
dc.contributor.authorDirks, Janen
dc.contributor.authorMack, Ulrichen
dc.contributor.authorPrasse, Antjeen
dc.contributor.authorSingh, Mahaviren
dc.contributor.authorLalvani, Ajiten
dc.contributor.authorSester, Martinaen
dc.date.accessioned2011-08-29T12:55:10Z-
dc.date.available2011-08-29T12:55:10Z-
dc.date.issued2011-
dc.identifier.citationWhole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states. 2011, 6 (3):e17813 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid21423578-
dc.identifier.doi10.1371/journal.pone.0017813-
dc.identifier.urihttp://hdl.handle.net/10033/141115-
dc.description.abstractT-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. tuberculosis infection. We postulated that IFN-γ and IL-2 cytokine profiles of antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB disease activity in vivo. Tuberculin (PPD), ESAT-6 and CFP-10 were used as stimuli to determine antigen-specific cytokine profiles in CD4 T cells from 24 patients with active TB and 28 patients with successfully treated TB using flow-cytometry. Moreover, 25 individuals with immunity consistent with latent M. tuberculosis infection and BCG-vaccination, respectively, were recruited. Although the frequency of cytokine secreting PPD reactive CD4 T cells was higher in patients with active TB compared to patients with treated TB (median 0.81% vs. 0.39% of CD4 T cells, p = 0.02), the overlap in frequencies precluded distinction between the groups on an individual basis. When assessing cytokine profiles, PPD specific CD4 T cells secreting both IFN-γ and IL-2 predominated in treated TB, latent infection and BCG-vaccination, whilst in active TB the cytokine profile was shifted towards cells secreting IFN-γ only (p<0.0001). Cytokine profiles of ESAT-6 or CFP-10 reactive CD4 T cells did not differ between the groups. Receiver operator characteristics (ROC) analysis revealed that frequencies of PPD specific IFN-γ/IL-2 dual-positive T cells below 56% were an accurate marker for active TB (specificity 100%, sensitivity 70%) enabling effective discrimination from non-active states. In conclusion, a frequency lower than 56% IFN-γ/IL-2 dual positive PPD-specific circulating CD4 T-cells is strongly indicative of active TB.en
dc.language.isoenen
dc.subject.meshAntigens, Bacterialen
dc.subject.meshBacterial Proteinsen
dc.subject.meshCD4-Positive T-Lymphocytesen
dc.subject.meshDemographyen
dc.subject.meshDiagnosis, Differentialen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshHumansen
dc.subject.meshInterferon-gammaen
dc.subject.meshInterleukin-2en
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshTuberculosisen
dc.titleWhole-blood flow-cytometric analysis of antigen-specific CD4 T-cell cytokine profiles distinguishes active tuberculosis from non-active states.en
dc.typeArticleen
dc.contributor.departmentDepartment of Internal Medicine IV, Saarland University, Homburg, Germany.en
dc.identifier.journalPloS oneen

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