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

Babu, S.; Bhat, S.Q.; Kumar, N.P.; Kumaraswami, V.; Nutman, T.B.

The Journal of Infectious Diseases; 2010; 201; 20–31.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: TST positivity is characterized by increased activity of regulatory T cells and a coincident downregulation of the Th17 response.

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