Whole-Blood Flow-Cytometric Analysis of Antigen-Specific CD4 T-Cell Cytokine Profiles Distinguishes Active Tuberculosis from Non-Active States

摘要: T-cell based IFN-γ release assays do not permit distinction of active tuberculosis (TB) from successfully treated disease or latent M. infection. We postulated that and IL-2 cytokine profiles antigen-specific T cells measured by flow-cytometry ex vivo might correlate with TB activity in vivo. Tuberculin (PPD), ESAT-6 CFP-10 were used as stimuli to determine CD4 24 patients 28 using flow-cytometry. Moreover, 25 individuals immunity consistent infection BCG-vaccination, respectively, recruited. Although the frequency secreting PPD reactive was higher compared (median 0.81% vs. 0.39% cells, p = 0.02), overlap frequencies precluded between groups on an individual basis. When assessing profiles, specific both predominated TB, whilst profile shifted towards only (p<0.0001). Cytokine did differ groups. Receiver operator characteristics (ROC) analysis revealed IFN-γ/IL-2 dual-positive below 56% accurate marker for (specificity 100%, sensitivity 70%) enabling effective discrimination non-active states. In conclusion, a lower than dual positive PPD-specific circulating T-cells is strongly indicative TB.