Regulatory T cells modulate Th17 responses in patients with positive tuberculin skin test results.

Abstract

The factors governing latency in tuberculosis are not well understood but appear to involve both the pathogen and the host. We have used tuberculin skin test (TST) positivity as a tool to study cytokine responses in latent tuberculosis. To identify the host factors that are important in the maintenance of TST positivity, we examined mycobacteria-specific immune responses of TST-positive (latent tuberculosis) or TST-negative individuals in South India, where TST positivity can define tuberculosis latency. Although purified protein derivative-specific and Mycobacterium tuberculosis culture filtrate antigen-specific Th1 and Th2 cytokines were not statistically significantly different between the 2 groups, the Th17 cytokines (interleukin 17 and interleukin 23) were statistically significantly decreased in TST-positive individuals, compared with those in TST-negative individuals. This Th17 cytokine modulation was associated with statistically significantly increased expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and Foxp3. Although CTLA-4 blockade failed to restore full production of interleukin 17 and interleukin 23 in TST-positive individuals, depletion of regulatory T cells significantly increased production of these cytokines. TST positivity is characterized by increased activity of regulatory T cells and a coincident down-regulation of the Th17 response.