Modulation of Th1/Tc1 and Th17/Tc17 responses in pulmonary tuberculosis by IL-20 subfamily of cytokines

Abstract

Although IL-10 is known to be an important cytokine in the immune response to TB, very little is known about the role of IL-20 subfamily of cytokines in the host response to TB. To identify the role of CD4⁺ T and CD8⁺ T cells producing IL-20 subfamily of cytokines in human TB, we enumerated the frequencies of IL-10, IL-19 and IL-24 expressing CD4⁺ and CD8⁺ T cells following Mtb-specific antigen stimulation of cells from individuals with pulmonary TB (PTB) and latent TB (LTB). We first demonstrated that Mtb-specific antigen induce an expansion of CD4⁺ and CD8⁺ T cells expressing IL-10, IL-19 and IL-24 in PTB and LTB individuals, with frequencies being significantly higher in PTB. Next, we demonstrated that IL-10, IL-19 and IL-24 play an important role in the regulation of CD4⁺ and CD8⁺ T cells expressing Th1/Tc1 and Th17/Tc17 cytokines in PTB but not LTB individuals. Thus, active PTB is characterized by an IL-10, IL-19 and IL-24 mediated down modulation of Th1/Tc1 and/or Th17/Tc17 cytokines in CD4⁺ and CD8⁺ T cell subsets. This suggests that the IL-20 subfamily of cytokines, similar to IL-10 might play a potentially crucial role in the modulation of T cell responses in active TB disease.

Keywords: IL-20 subfamily cytokines; Latent tuberculosis; T cell responses; Tuberculosis.