Differential Glycosylation of Th1 and Th2 cells selectively regulates susceptibility to galectin-1-induced cell death

MARTA A. TOSCANO, JUAN M. ILARREGUI, GERMÁN A. BIANCO, NATALIA RUBINSTEIN, NORBERTO W. ZWIRNER, GABRIEL A. RABINOVICH

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología ALAI 2005; 2005

Latin American Society of Immunology

Differential glycosylation of Th1 and Th2 cells selectively regulates susceptibility to galectin-1-induced cell death   M Toscano, J Ilarregui, G Bianco, N Rubinstein, N Zwirner & G Rabinovich. Lab Inmunogenética Fac Medicina, UBA   Therapeutic administration of galectin-1 (Gal-1) in experimental chronic inflammation results in a Th1 to Th2 shift with selective elimination of antigen-activated T cells. The aim of this study was to investigate the differential susceptibility of human and murine T helper cells to Gal-1-induced apoptosis. Here we show that Th1- and Th2-promoting signals can differentially regulate the glycosylation pattern of T helper cells and modulate susceptibility to Gal-1. While human Th1 cells express the repertoire of cell surface glycans that are critical for Gal-1 binding and death, Th2 cells are protected from Gal-1 through differential sialylation of N- and O-glycans on cell surface glycoproteins (p<0.05). To validate our findings in vivo, we used a model of antigen-specific Th1 and Th2 responses. Dendritic cells (DC) pulsed with P acnes (Pa) promote Th1 responses when injected into naive mice, whereas DC pulsed with S mansoni egg antigen (SEA) induce Th2 responses. Consistent with in vitro Th1-polarized cells, in vivo generated Pa-specific Th1 cells exhibited the cell surface glycans required for Gal-1 binding and death. In contrast, SEA-specific Th2 cells, which exhibit sialylated N- and O-glycans, were resistant to Gal-1 (p<0.05) similarly to in vitro human Th2 cells. Our findings identify a novel mechanism, based on differential glycosylation of Th1 and Th2 cell subsets, by which Gal-1 may preferentially eliminate antigen-specific Th1 effectors with critical implications for immunotherapy.