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Multifunctional Analysis of CD4+ T-Cell Response as Immune-Based Model for Tuberculosis Detection.

Lichtner M, Mascia C, Sauzullo I, Mengoni F, Vita S, Marocco R, Belvisi V, Russo G, Vullo V, Mastroianni CM - J Immunol Res (2015)

Bottom Line: Among TB-infected subjects, the frequencies of multifunctional CD4(+) T cells, simultaneously producing all 3 cytokines, are lower in active TB than LTBI subjects (P = 0.003).Thus, assigning to triple-positive CD4(+) T cells a cut-off <0.182%, TB-infected individuals could be classified as active TB subjects (<0.182%) or LTBI subjects (>0.182%).The magnitude of CD8(+) T-cell responses showed no differences between active TB and LTBI.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy ; Infectious Diseases Unit, Sapienza University, Corso della Repubblica 79, 04100 Latina, Italy.

ABSTRACT
Mono- and multifunctional specific CD4(+) and CD8(+) T-cell responses were evaluated to improve the immune-based detection of active tuberculosis (TB) and latent infection (LTBI). We applied flow cytometry to investigate cytokines profile (IFN-γ, TNF-α, and IL-2) of T cells after stimulation with TB antigens in 28 TB-infected subjects (18 active TB and 10 LTBI) and 10 uninfected controls. Cytokines production by CD4(+) T cells at single-cell levels was higher in TB-infected subjects than uninfected controls (P < 0.0001). Assigning to activated CD4(+) T cells, producing any of the three cytokines, a cut-off >0.45%, it was possible to differentiate TB-infected (>0.45%) by uninfected subjects (<0.45%). Among TB-infected subjects, the frequencies of multifunctional CD4(+) T cells, simultaneously producing all 3 cytokines, are lower in active TB than LTBI subjects (P = 0.003). Thus, assigning to triple-positive CD4(+) T cells a cut-off <0.182%, TB-infected individuals could be classified as active TB subjects (<0.182%) or LTBI subjects (>0.182%). The magnitude of CD8(+) T-cell responses showed no differences between active TB and LTBI. Multifunctional CD4(+) T-cell responses could have the potential to identify at single time point subjects without TB infection and patients having active or latent TB.

No MeSH data available.


Related in: MedlinePlus

Multifunctional cytokine analysis of Mtb-specific CD8+ T cells. (a) Frequency of Mtb-specific CD8+ T cells producing all combinations of IFN-γ, IL-2, and TNF-α in active TB patients (n = 18, black circles) and in LTBI patients (n = 10, white circles). Horizontal bars represent the median values. Statistical analysis was performed using Mann-Whitney test. (b) Pie charts represent the relative proportions of cytokine-producing T-cell subsets in each group after Mtb-specific stimulation. A key to colours used in the pie charts is shown at the bottom of the panel (a).
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fig6: Multifunctional cytokine analysis of Mtb-specific CD8+ T cells. (a) Frequency of Mtb-specific CD8+ T cells producing all combinations of IFN-γ, IL-2, and TNF-α in active TB patients (n = 18, black circles) and in LTBI patients (n = 10, white circles). Horizontal bars represent the median values. Statistical analysis was performed using Mann-Whitney test. (b) Pie charts represent the relative proportions of cytokine-producing T-cell subsets in each group after Mtb-specific stimulation. A key to colours used in the pie charts is shown at the bottom of the panel (a).

Mentions: As regards the cytokine profiles of Mtb-specific CD8+ T cells, we found no significant differences between active TB and LTBI subjects (P > 0.05 for each CD8+ T-cell subset by Mann-Whitney test; Figure 6(a)). Still, observing the pie charts (Figure 6(b)) the proportions of single-, double-, or triple-cytokine-secreting CD8+ T-cell subsets were comparable between two groups of individuals.


Multifunctional Analysis of CD4+ T-Cell Response as Immune-Based Model for Tuberculosis Detection.

Lichtner M, Mascia C, Sauzullo I, Mengoni F, Vita S, Marocco R, Belvisi V, Russo G, Vullo V, Mastroianni CM - J Immunol Res (2015)

Multifunctional cytokine analysis of Mtb-specific CD8+ T cells. (a) Frequency of Mtb-specific CD8+ T cells producing all combinations of IFN-γ, IL-2, and TNF-α in active TB patients (n = 18, black circles) and in LTBI patients (n = 10, white circles). Horizontal bars represent the median values. Statistical analysis was performed using Mann-Whitney test. (b) Pie charts represent the relative proportions of cytokine-producing T-cell subsets in each group after Mtb-specific stimulation. A key to colours used in the pie charts is shown at the bottom of the panel (a).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4539126&req=5

fig6: Multifunctional cytokine analysis of Mtb-specific CD8+ T cells. (a) Frequency of Mtb-specific CD8+ T cells producing all combinations of IFN-γ, IL-2, and TNF-α in active TB patients (n = 18, black circles) and in LTBI patients (n = 10, white circles). Horizontal bars represent the median values. Statistical analysis was performed using Mann-Whitney test. (b) Pie charts represent the relative proportions of cytokine-producing T-cell subsets in each group after Mtb-specific stimulation. A key to colours used in the pie charts is shown at the bottom of the panel (a).
Mentions: As regards the cytokine profiles of Mtb-specific CD8+ T cells, we found no significant differences between active TB and LTBI subjects (P > 0.05 for each CD8+ T-cell subset by Mann-Whitney test; Figure 6(a)). Still, observing the pie charts (Figure 6(b)) the proportions of single-, double-, or triple-cytokine-secreting CD8+ T-cell subsets were comparable between two groups of individuals.

Bottom Line: Among TB-infected subjects, the frequencies of multifunctional CD4(+) T cells, simultaneously producing all 3 cytokines, are lower in active TB than LTBI subjects (P = 0.003).Thus, assigning to triple-positive CD4(+) T cells a cut-off <0.182%, TB-infected individuals could be classified as active TB subjects (<0.182%) or LTBI subjects (>0.182%).The magnitude of CD8(+) T-cell responses showed no differences between active TB and LTBI.

View Article: PubMed Central - PubMed

Affiliation: Department of Public Health and Infectious Diseases, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy ; Infectious Diseases Unit, Sapienza University, Corso della Repubblica 79, 04100 Latina, Italy.

ABSTRACT
Mono- and multifunctional specific CD4(+) and CD8(+) T-cell responses were evaluated to improve the immune-based detection of active tuberculosis (TB) and latent infection (LTBI). We applied flow cytometry to investigate cytokines profile (IFN-γ, TNF-α, and IL-2) of T cells after stimulation with TB antigens in 28 TB-infected subjects (18 active TB and 10 LTBI) and 10 uninfected controls. Cytokines production by CD4(+) T cells at single-cell levels was higher in TB-infected subjects than uninfected controls (P < 0.0001). Assigning to activated CD4(+) T cells, producing any of the three cytokines, a cut-off >0.45%, it was possible to differentiate TB-infected (>0.45%) by uninfected subjects (<0.45%). Among TB-infected subjects, the frequencies of multifunctional CD4(+) T cells, simultaneously producing all 3 cytokines, are lower in active TB than LTBI subjects (P = 0.003). Thus, assigning to triple-positive CD4(+) T cells a cut-off <0.182%, TB-infected individuals could be classified as active TB subjects (<0.182%) or LTBI subjects (>0.182%). The magnitude of CD8(+) T-cell responses showed no differences between active TB and LTBI. Multifunctional CD4(+) T-cell responses could have the potential to identify at single time point subjects without TB infection and patients having active or latent TB.

No MeSH data available.


Related in: MedlinePlus