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Multifunctional CD4+T cells correlate with active Mycobacterium tuberculosis infection

  • Autori: Caccamo N; Guggino G; Joosten SA; Gelsomino G; Di Carlo P; Titone Lanza di Scalea L; Galati D; Bocchino M; Matarese A; Salerno A; Sanduzzi A; Franken WP; Ottenhoff TH; Dieli F
  • Anno di pubblicazione: 2010
  • Tipologia: Articolo in rivista (Articolo in rivista)
  • Parole Chiave: CD4+ T cells ; Cytokines; Mycobacterium tuberculosis infection; Tuberculosis disease.
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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