Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection

TY - JOUR

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 -