Paradoxical high regulatory T cell activity in Behçet's disease

CD4+CD25(bright) T cells and NKT cells are potent immunoregulatory cells and are therefore attractive targets for immunotherapy. The possibility of modulating CD4+CD25(bright) T cell function using NKT cells, and vice versa, reveals a new route for harnessing suppressor T cells with therapeutic properties. However, the questions of where, when and how NKT cells interact with CD4+CD25(bright) T cells are still unknown. Disease studies have investigated the regulatory properties of these T-cell subsets independently of each other. Recent reports have provided evidence for cross-talk between CD4+CD25(bright) T cells and NKT cells and consequently, the immunoregulatory networks are seen in a new perspective. Activated NKT cells seem to modulate quantitatively and qualitatively CD4+CD25(bright) T cell function through IL-2-dependent mechanisms, whereas CD4+CD25(bright) T cells can suppress the proliferation, cytokine release and cytotoxic activity of NKT cells by cell-contact-dependent mechanisms. Importantly, CD4+CD25(bright) T cells and NKT cells share crucial signalling pathways that could be responsible for immune dysregulations in Behçet's disease (BD). The advances in our understanding of the interactions between distinct subsets of regulatory T cells might unveil new waves for modulating these cells with the inflammatory process in BD.