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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

Proposed immune-based model for detection of active and latent TB. Taking into account the analysis of activated CD4+ T cells, it is possible to differentiate Mtb-infected subjects (>0.45%) by uninfected subjects (<0.45%). With the analysis of multifunctional CD4+ T cells, simultaneously producing all 3 cytokines, infected individuals may be classified as active TB subjects (<0.182%) or as LTBI subjects (>0.182%).
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Related In: Results  -  Collection


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fig7: Proposed immune-based model for detection of active and latent TB. Taking into account the analysis of activated CD4+ T cells, it is possible to differentiate Mtb-infected subjects (>0.45%) by uninfected subjects (<0.45%). With the analysis of multifunctional CD4+ T cells, simultaneously producing all 3 cytokines, infected individuals may be classified as active TB subjects (<0.182%) or as LTBI subjects (>0.182%).

Mentions: The present study has some limitations, such as the relatively small number of patients within each clinical group and the lack of a prospective analysis. Nevertheless, the ICCFC assessment of multifunctional Mob-specific CD4+ T cells enabled us to determine the different clinical stage of TB infection. In this respect we propose an immune model (Figure 7) which, with a cut-off of 0.45% for activated CD4+ T cells, may initially discriminate Mtb-infected (active TB and LTBI) patients (>0.45%) from uninfected subjects (<0.45%) with a specificity of 100%. Then, the infected individuals may be classified as active TB subjects if they showed frequencies of triple-positive T cells less than 0.182% and as LTBI subjects if the frequencies of triple-positive T cells are instead above 0.182% with a sensitivity of 77.78% and a specificity of 70%.


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)

Proposed immune-based model for detection of active and latent TB. Taking into account the analysis of activated CD4+ T cells, it is possible to differentiate Mtb-infected subjects (>0.45%) by uninfected subjects (<0.45%). With the analysis of multifunctional CD4+ T cells, simultaneously producing all 3 cytokines, infected individuals may be classified as active TB subjects (<0.182%) or as LTBI subjects (>0.182%).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig7: Proposed immune-based model for detection of active and latent TB. Taking into account the analysis of activated CD4+ T cells, it is possible to differentiate Mtb-infected subjects (>0.45%) by uninfected subjects (<0.45%). With the analysis of multifunctional CD4+ T cells, simultaneously producing all 3 cytokines, infected individuals may be classified as active TB subjects (<0.182%) or as LTBI subjects (>0.182%).
Mentions: The present study has some limitations, such as the relatively small number of patients within each clinical group and the lack of a prospective analysis. Nevertheless, the ICCFC assessment of multifunctional Mob-specific CD4+ T cells enabled us to determine the different clinical stage of TB infection. In this respect we propose an immune model (Figure 7) which, with a cut-off of 0.45% for activated CD4+ T cells, may initially discriminate Mtb-infected (active TB and LTBI) patients (>0.45%) from uninfected subjects (<0.45%) with a specificity of 100%. Then, the infected individuals may be classified as active TB subjects if they showed frequencies of triple-positive T cells less than 0.182% and as LTBI subjects if the frequencies of triple-positive T cells are instead above 0.182% with a sensitivity of 77.78% and a specificity of 70%.

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