Tim-3-Galectin-9 Pathway Involves the Suppression Induced by CD4+CD25+ Regulatory T Cells

CD4(+)CD25(+) regulatory T cells (Tregs) are considered to play a key role as suppressors of immune-mediated reactions. The mechanisms of this suppression in animals and patients with autoimmune, allergic or oncogenic diseases have been investigated under various conditions. However, the precise mode of suppression by CD4(+)CD25(+) Tregs is still not clear. In this report, Tim-3-Galectin-9 pathway was explored as one of the mechanisms for the suppression and cytotoxicity induced by Tregs. Here, we demonstrated that Galectin-9 was expressed on CD4(+)CD25(+) Tregs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. Interestingly, blocking Tim-3-Galectin-9 pathway resulted in an obvious decreased suppression activity of Tregs and enhanced Th1 cytokine level in vitro. Furthermore, blocking Tim-3-Galectin-9 pathway negated prolonged survival of allogeneic skin grafts induced by CD4(+)CD25(+) Tregs in vivo. Our results suggest that Tim-3-Galectin-9 pathway involves the function of CD4(+)CD25(+) Tregs.