Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection |
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Authors: | 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 Francesco Dieli |
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Institution: | 1. Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, University of Palermo, Palermo, Italy;2. Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands;3. Dipartimento di Medicina Clinica e delle Patologie Emergenti, University of Palermo, Palermo, Italy;4. TB Infection Screening Unit, Department of Clinical and Experimental Medicine, University of Naples “Federico II”, Monaldi Hospital, Naples, Italy;5. Dipartimento di Biopatologia e Biotecnologie Mediche e Forensi, University of Palermo, Palermo, ItalyThese authors have contributed equally to this work. |
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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‐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. |
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Keywords: | CD4+ T cells Cytokines Mycobacterium tuberculosis infection Tuberculosis disease |
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