No abstract

Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses.

Distinct IFN-gamma and IL-2 profiles of antigen-specific CD4+ T cells have recently been associated with different clinical disease states and antigen loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis antigen-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis, when bacterial and antigen load are high, and after curative treatment when antigen load is reduced. Frequencies of M. tuberculosis antigen-specific IFN-gamma-secreting T cells declined during 28 months of follow up with an average percentage decline of 5.8% per year (P=0.005), whilst frequencies of antigen-specific IL-2-secreting T cells increased during treatment (P=0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma and IL-2-secreting cells over 28 months. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single cell level revealed a co-dominance of IFN-gamma-only and IFN-gamma/IL-2 dual-secreting CD4+ T cells in active disease which shifted to dominance of IFN-gamma/IL-2-secreting CD4+ T cells and newly detectable IL-2-only-secreting CD4+ T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis, which now requires validation in larger prospective studies.

The ELISpot(PLUS) assay is more sensitive than standard ELISpot and, when used in combination with tuberculin skin testing, enables rapid exclusion of active infection in patients with moderate to high pretest probability of tuberculosis.