Multifunctional CD4⁺ T cells correlate with active Mycobacterium tuberculosis infection

• Published in: European journal of immunology Vol. 40; no. 8; pp. 2211 - 2220
• Main Authors: Caccamo, Nadia, Guggino, Giuliana, Joosten, Simone A, Gelsomino, Giuseppe, Di Carlo, Paola, Titone, Lucina, Galati, Domenico, Bocchino, Marialuisa, Matarese, Alessandro, Salerno, Alfredo, Sanduzzi, Alessandro, Franken, Willeke P.J, Ottenhoff, Tom H.M, Dieli, Francesco
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.08.2010; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Acute Disease; Acyltransferases - immunology; Adult; Antigens, Bacterial - immunology; Bacterial Load - immunology; Bacterial Proteins - immunology; CD4+ T cells; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - microbiology; CD4-Positive T-Lymphocytes - pathology; Cell Separation; Chronic Disease; Cytokines; Cytokines - secretion; Flow Cytometry; Humans; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mycobacterium tuberculosis - immunology; Mycobacterium tuberculosis - pathogenicity; Mycobacterium tuberculosis infection; Tuberculosis; Tuberculosis disease; Tuberculosis, Pulmonary - diagnosis; Tuberculosis, Pulmonary - immunology
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.201040455

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.