Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death

Regulated glycosylation controls T cell processes, including activation, differentiation and homing by creating or masking ligands for endogenous lectins. Here we show that stimuli promoting T helper type 1 (T H 1), T H 2 or interleukin 17–producing T helper (T H -17) differentiation can differentially regulate the glycosylation pattern of T helper cells and modulate their susceptibility to galectin-1, a glycan-binding protein with anti-inflammatory activity. Although T H 1- and T H -17–differentiated cells expressed the repertoire of cell surface glycans critical for galectin-1–induced cell death, T H 2 cells were protected from galectin-1 through differential sialylation of cell surface glycoproteins. Consistent with those findings, galectin-1–deficient mice developed greater T H 1 and T H -17 responses and enhanced susceptibility to autoimmune neuroinflammation. Our findings identify a molecular link among differential glycosylation of T helper cells, susceptibility to cell death and termination of the inflammatory response.