Multifunctional cytokine and T cell memory phenotype profiles differ in active versus cured tuberculosis.

Abstract

Abstract Tuberculosis, one of the most prevalent and deadliest infectious diseases worldwide, requires long-term multidrug treatment regimens for curing active clinical disease. However, a diagnostic method for identifying successful cure from TB disease following anti-TB chemotherapy remains elusive. The overall goal of this study was to assess differential patterns of cytokine production and memory T cell phenotypes to distinguish between active TB subjects and remotely cured TB individuals. Using peripheral blood mononuclear cells from subjects enrolled in a TB household contact study established in Vitória, Brazil, cells were stimulated ex vivo with TB antigens and evaluated using multi-parametric flow cytometry. Total cytokine and multifunctional cytokine analyses revealed an increase in the proportion of IL-17 producing CD4+ T cells in active TB subjects, while cured TB subjects showed a clear dominance of cells producing IFNγ and IL-2 or TNFα. Comparison of memory phenotypes revealed differences between proportions of several CD4+ T cell memory subsets, with an effector memory dominance in cured TB compared to an increased stem cell memory representation in active TB. Increased expression of exhaustion marker PD-1 in advanced stages of memory cell differentiation suggested its possible use as a surrogate indicator of memory subset fluxes, with possible application as a biomarker for distinguishing differences between cured TB and active TB individuals.