Flow cytometric measurements of TB‐specific T cells comparing with QuantiFERON‐TB gold

Won, Dong Il; Park, Jung Ran

doi:10.1002/cyto.b.20503

Cited by 15 publications

(17 citation statements)

References 27 publications

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“…Other studies have previously investigated the ability of antigen-specific T cells to produce simultaneously a range of cytokines in human TB [24][25][26][27][28][29][30][31][32][33], but contrasting data regarding the distribution of cytokine-producing CD4 + T cell subsets in different stages of TB have been reported. However, it has been suggested that combined analyses of different cytokines produced by multi-functional T cells may aid distinction between active TB patients and subjects with LTBI [30,32].…”

Section: Discussionmentioning

confidence: 99%

Multi-functional flow cytometry analysis of CD4+ T cells as an immune biomarker for latent tuberculosis status in patients treated with tumour necrosis factor (TNF) antagonists

Sauzullo

Mengoni

Ermocida

et al. 2014

Clinical and Experimental Immunology

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Although monitoring tuberculosis (TB) infection during long-term treatment with tumour necrosis factor (TNF) antagonists is of great importance, no monitoring strategy has yet proved successful. Indeed, even the newly proposed interferon-gamma release assays (IGRAs) are known to produce dynamic changes in IFN-γ plasma levels, making them unreliable indicators of patients' pathological/clinical status. We used intracellular cytokine flow cytometry (ICCFC) to investigate the performance of multi-functional CD4(+) T cells producing IFN-γ, interleukin (IL)-2 and/or TNF in response to Mycobacterium tuberculosis-specific antigens in subjects treated with TNF antagonists. Patients were classified into three groups based on their TB status before commencement of treatment and on IFN-γ level fluctuations evaluated by IGRA during a 36-month follow-up period. The cytokine profile of M. tuberculosis-specific CD4(+) T cells showed that latent tuberculosis infection (LTBI) subjects had a higher frequency of double-positive IFN-γ(+) IL-2(+) CD4(+) T cells and triple-positive IFN-γ(+) IL-2(+) TNF(+) CD4(+) T cells compared to those without LTBI, who showed IFN-γ-level fluctuations over time. In contrast, this latter group of patients showed similar proportions of cells producing IFN-γ alone, IL-2 alone and IL-2 in combination with TNF in response to M. tuberculosis-specific antigens. It therefore appears that patients with and without LTBI infection are characterized by different intracellular cytokine profiles. This is the first study evaluating ICCFC in patients treated with TNF antagonists, and suggests that multi-functional analysis of CD4(+) T cells could be useful for ruling out TB infection in patients classified at screening as LTBI-negative but who show IGRA fluctuations under long-term TNF antagonist treatment.

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Section: Discussionmentioning

confidence: 99%

Multi-functional flow cytometry analysis of CD4+ T cells as an immune biomarker for latent tuberculosis status in patients treated with tumour necrosis factor (TNF) antagonists

Sauzullo

Mengoni

Ermocida

et al. 2014

Clinical and Experimental Immunology

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“…No significant differences between untreated and treated LTBI subjects in terms of Mtb-specific CD8 + T cell cytokine profiles (p > 0.05) were identified. The significant changes in the cytokine profiles of Mtb-specific T cells after INH therapy suggest that analysis IGRA to detect TB infection [17][18][19][20]. Indeed, ICCFC has been reported to improve discrimination between active TB and LTBI [10][11][12][13][14][15][16] and to enable more reliable monitoring of responses to TB treatment [11-13, 21, 22].…”

Section: Introductionmentioning

confidence: 98%

Treatment of latent tuberculosis infection induces changes in multifunctional Mycobacterium tuberculosis-specific CD4+ T cells

Sauzullo¹,

Mengoni²,

Mascia³

et al. 2015

Med Microbiol Immunol

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To ascertain whether multiparametric flow cytometry assessment of multifunctional Mycobacterium tuberculosis (Mtb)-specific CD4(+) and CD8(+) T cells can distinguish between untreated and treated patients with latent tuberculosis infection (LTBI), we enrolled 14 LTBI subjects treated with isoniazid (INH) therapy, 16 untreated LTBI patients, and 25 healthy controls. The analysis of mono-functional CD4(+) and CD8(+) T cells producing single cytokines showed significant differences only between uninfected and infected LTBI subjects (both treated and untreated). Conversely, the analysis of multifunctional CD4(+) T cells revealed a significant reduction in the frequency of two CD4(+) T cells subsets, those producing IFN-γ, IL-2, and TNF-α simultaneously (triple positive; p = 0.005) and those producing IL-2 alone (p = 0.0359), as well as a shift towards T cells producing only one cytokine in treated as compared to untreated LTBI subjects. Assigning a triple-positive CD4(+) T cells a cut-off >0.082 %, 94 % of untreated LTBI patients were scored as positive, as compared to only 28 % of treated LTBI patients and none of the healthy controls. No significant differences between untreated and treated LTBI subjects in terms of Mtb-specific CD8(+) T cell cytokine profiles (p > 0.05) were identified. The significant changes in the cytokine profiles of Mtb-specific T cells after INH therapy suggest that analysis of multifunctional T cells may be a promising means for the monitoring of LTBI treatment success.

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“…The tuberculin skin test (TST) does not measure antigen-specific CD4 + or CD8 + T-cells and often gives false results [23]. The IFN-gamma release assays-IGRA, such as Quantiferon-Gold (QFT) and T-SPOT.TB, however, are more appropriate in detecting TB-specific responses [24]. The three antigens composing the QFT test, ESAT-6, CFP-10, and TB7.7, are represented as peptides and detected using whole blood [25].…”

mentioning

confidence: 99%

“…New assays to detect CD4 + and CD8 + T-cell responses after MTB infection includes cell specific detection systems, such as flow cytometry and enzyme based assays (such as ELISPOT) [24,[32][33][34][35][36][37]. These assays will quantitatively and qualitatively measure specific CD4 + and/or CD8 + T-cell responses that are specific for MTB.…”

mentioning

confidence: 99%

Revisiting the Current Assays Associated to Host Immune Responses Against Tuberculosis Infection

Mothé

Antas²

2015

J Anc Dis Prev Rem

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Flow cytometric measurements of TB‐specific T cells comparing with QuantiFERON‐TB gold

Cited by 15 publications

References 27 publications

Multi-functional flow cytometry analysis of CD4+ T cells as an immune biomarker for latent tuberculosis status in patients treated with tumour necrosis factor (TNF) antagonists

Multi-functional flow cytometry analysis of CD4+ T cells as an immune biomarker for latent tuberculosis status in patients treated with tumour necrosis factor (TNF) antagonists

Treatment of latent tuberculosis infection induces changes in multifunctional Mycobacterium tuberculosis-specific CD4+ T cells

Revisiting the Current Assays Associated to Host Immune Responses Against Tuberculosis Infection

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