Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection

Nadia Rosalia Caccamo, Giuliana Guggino, Francesco Dieli, Paola Di Carlo, 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

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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
Lingua originaleEnglish
Numero di pagine33
RivistaEuropean Journal of Immunology
Volume2010-06
Stato di pubblicazionePublished - 2010

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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Caccamo, N. R., Guggino, G., Dieli, F., Di Carlo, P., Titone Lanza Di Scalea, L., Salerno, A., Franken, W. P. J., Matarese, A., Galati, D., Joosten, S. A., Bocchino, M., Sanduzzi, A., Ottenhoff, T. H. M., & Gelsomino, G. (2010). Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection. European Journal of Immunology, 2010-06.