Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection

Nadia Rosalia Caccamo, Giuliana Guggino, Paola Di Carlo, Francesco Dieli, Lucina Titone Lanza Di Scalea, Alfredo Salerno, Willeke P. J. Franken, Alessandro Matarese, Domenico Galati, Simone A. Joosten, Marialuisa Bocchino, Alessandro Sanduzzi, Tom H. M. Ottenhoff, Giuseppe Gelsomino

Risultato della ricerca: Article

214 Citazioni (Scopus)

Abstract

Th1 CD4+T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4+T cells in individuals with latent (LTBI) and active (TB) tuberculosis. We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. In contrast, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4+T cell subsets. Proportions of the other double or single CD4+T cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of Mycobacterium tuberculosis-specific CD4+T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4+T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy
Lingua originaleEnglish
Numero di pagine33
RivistaDefault journal
Volume2010-06
Stato di pubblicazionePublished - 2010

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Mycobacterium Infections
Mycobacterium tuberculosis
Interleukin-2
T-Lymphocytes
Tumor Necrosis Factor-alpha
Bacterial Load
T-Lymphocyte Subsets
Flow Cytometry
Tuberculosis
Cytokines
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection. / Caccamo, Nadia Rosalia; Guggino, Giuliana; Di Carlo, Paola; Dieli, Francesco; Titone Lanza Di Scalea, Lucina; Salerno, Alfredo; Franken, Willeke P. J.; Matarese, Alessandro; Galati, Domenico; Joosten, Simone A.; Bocchino, Marialuisa; Sanduzzi, Alessandro; Ottenhoff, Tom H. M.; Gelsomino, Giuseppe.

In: Default journal, Vol. 2010-06, 2010.

Risultato della ricerca: Article

Caccamo, NR, Guggino, G, Di Carlo, P, Dieli, F, Titone Lanza Di Scalea, L, Salerno, A, Franken, WPJ, Matarese, A, Galati, D, Joosten, SA, Bocchino, M, Sanduzzi, A, Ottenhoff, THM & Gelsomino, G 2010, 'Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection', Default journal, vol. 2010-06.
Caccamo, Nadia Rosalia ; Guggino, Giuliana ; Di Carlo, Paola ; Dieli, Francesco ; Titone Lanza Di Scalea, Lucina ; Salerno, Alfredo ; Franken, Willeke P. J. ; Matarese, Alessandro ; Galati, Domenico ; Joosten, Simone A. ; Bocchino, Marialuisa ; Sanduzzi, Alessandro ; Ottenhoff, Tom H. M. ; Gelsomino, Giuseppe. / Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection. In: Default journal. 2010 ; Vol. 2010-06.
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abstract = "Th1 CD4+T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4+T cells in individuals with latent (LTBI) and active (TB) tuberculosis. We found that triple expressors, while detectable in 85-90{\%}TB patients, were only present in 10-15{\%} of LTBI subjects. In contrast, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4+T cell subsets. Proportions of the other double or single CD4+T cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of Mycobacterium tuberculosis-specific CD4+T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4+T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy",
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T1 - Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection

AU - Caccamo, Nadia Rosalia

AU - Guggino, Giuliana

AU - Di Carlo, Paola

AU - Dieli, Francesco

AU - Titone Lanza Di Scalea, Lucina

AU - Salerno, Alfredo

AU - Franken, Willeke P. J.

AU - Matarese, Alessandro

AU - Galati, Domenico

AU - Joosten, Simone A.

AU - Bocchino, Marialuisa

AU - Sanduzzi, Alessandro

AU - Ottenhoff, Tom H. M.

AU - Gelsomino, Giuseppe

PY - 2010

Y1 - 2010

N2 - Th1 CD4+T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4+T cells in individuals with latent (LTBI) and active (TB) tuberculosis. We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. In contrast, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4+T cell subsets. Proportions of the other double or single CD4+T cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of Mycobacterium tuberculosis-specific CD4+T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4+T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy

AB - Th1 CD4+T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4+T cells in individuals with latent (LTBI) and active (TB) tuberculosis. We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. In contrast, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4+T cell subsets. Proportions of the other double or single CD4+T cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of Mycobacterium tuberculosis-specific CD4+T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4+T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy

KW - CD4+ T cells

KW - Cytokines

KW - Mycobacterium tuberculosis infection

KW - Tuberculosis disease.

UR - http://hdl.handle.net/10447/50776

M3 - Article

VL - 2010-06

JO - Default journal

JF - Default journal

ER -