Multifunctional Analysis of CD4+ T-Cell Response as Immune-Based Model for Tuberculosis Detection

• Main Authors: Miriam Lichtner, Claudia Mascia, Ilaria Sauzullo, Fabio Mengoni, Serena Vita, Raffaella Marocco, Valeria Belvisi, Gianluca Russo, Vincenzo Vullo, Claudio M. Mastroianni
• Format: Article
• Language: English
• Published: Hindawi Limited 2015-01-01
• Series: Journal of Immunology Research
• Online Access: http://dx.doi.org/10.1155/2015/217287

Mono- and multifunctional specific CD4+ and CD8+ T-cell responses were evaluated to improve the immune-based detection of active tuberculosis (TB) and latent infection (LTBI). We applied flow cytometry to investigate cytokines profile (IFN-γ, TNF-α, and IL-2) of T cells after stimulation with TB antigens in 28 TB-infected subjects (18 active TB and 10 LTBI) and 10 uninfected controls. Cytokines production by CD4+ T cells at single-cell levels was higher in TB-infected subjects than uninfected controls P<0.0001. Assigning to activated CD4+ T cells, producing any of the three cytokines, a cut-off >0.45%, it was possible to differentiate TB-infected (>0.45%) by uninfected subjects (<0.45%). Among TB-infected subjects, the frequencies of multifunctional CD4+ T cells, simultaneously producing all 3 cytokines, are lower in active TB than LTBI subjects P=0.003. Thus, assigning to triple-positive CD4+ T cells a cut-off <0.182%, TB-infected individuals could be classified as active TB subjects (<0.182%) or LTBI subjects (>0.182%). The magnitude of CD8+ T-cell responses showed no differences between active TB and LTBI. Multifunctional CD4+ T-cell responses could have the potential to identify at single time point subjects without TB infection and patients having active or latent TB.