Multifunctional analysis of CD4+ T-cell response as immune-based model for tuberculosis detection

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. © 2015 miriam lichtner et al.