NKG2D-Dependent IL-17 Production by Human T Cells in Response to an Intracellular Pathogen

Abstract

We studied the factors that control IL-17 production in human Mycobacterium tuberculosis infection. CD4+ cells from healthy tuberculin reactors produced IL-17 in response to autologous M. tuberculosis-stimulated monocytes, and most IL-17+ cells were Ag experienced, CD4+CD62L−. IL-17 production by CD4+ cells was inhibited by anti-IL-23, but not by Abs to IL-1, IL-6, or TGF-β. Anti-NKG2D reduced IL-17 production and the frequency of CD4+CD62− IL-17+ cells, suggesting that NKG2D stimulates IL-17 production. CD4+NKG2D+ cells did not produce IL-17. Monocytes and alveolar macrophages from healthy donors produced IL-23 in response to M. tuberculosis. Addition of CD4+ cells markedly enhanced IL-23 production by M. tuberculosis-stimulated monocytes, and this was inhibited by anti-NKG2D and by Abs to UL-16 binding protein (ULB)1, a ligand for NKG2D on APCs. We conclude that binding of NKG2D to UL-16 binding protein (ULB)1 contributes to IL-23-dependent IL-17 production by CD4+ cells in human M. tuberculosis infection.