Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection

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

Research output: Contribution to journalArticle

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-γ/IL-2/TNF-α triple expressors, IFN-γ/IL-2, IFN-γ/TNF-α or TNF-α/IL-2 double expressors or IFN-γ, IL-2 or TNF-α single expressors) of CD4+ T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-γ double and IFN-γ 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-γ, IL-2 and TNF-α profiles of M. 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-infected 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.

Original languageEnglish
Pages (from-to)2211-2220
Number of pages10
JournalEuropean Journal of Immunology
Volume40
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • CD4 T cells
  • Cytokines
  • Mycobacterium tuberculosis infection
  • Tuberculosis disease

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Caccamo, N., Guggino, G., Joosten, S. A., Gelsomino, G., Di Carlo, P., Titone, L., Galati, D., Bocchino, M., Matarese, A., Salerno, A., Sanduzzi, A., Franken, W. P. J., Ottenhoff, T. H. M., & Dieli, F. (2010). Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection. European Journal of Immunology, 40(8), 2211-2220. https://doi.org/10.1002/eji.201040455