Abstract:

Galectins are a family of carbohydrate binding proteins that have been conserved through evolution. Galectin-1 is a secreted homodimeric member of this family, with two carbohydrate-binding domains capable of crosslinking ligands. Galectin-1 recognizes N-acetyllactosamine but only binds with high affinity to chains of multiple N-acetyllactosamine disaccharides. These chains can be presented on either O-linked or N-linked glycans that decorate cell surface proteins. Galectin-1 is expressed in thymus, where T cells develop, as well as in spleen and lymph nodes where T cells function. Several cell surface proteins on T cells can bind galectin-1 including CD3, CD4, CD7, CD43, and CD45. Binding of galectin-1 to T cell surface proteins can cause apoptosis in some T cell populations. Our studies investigated a function for endogenous galectin-1 expression in the thymic selection of CD4+ T cells. We used galectin-1 +/+ or -/- TCR transgenic mouse models of positive and negative thymic selection, and analyzed cell populations present by flow cytometry. In the thymus of positively selecting mice, lack of galectin-1 expression resulted in a higher percentage of double negative thymocytes that were in stage DN4. In the spleen of negative selecting mice, lack of galectin-1 expression led to a higher percentage of CD4-CD8- cells that expressed the transgenic TCR and CD3, escapees from negative selection in the thymus. Several mice of our negative selection model showed signs of autoimmunity; however, we did not see an effect of endogenous galectin-1 expression on severity of autoimmune symptoms. Experiments on galectin-1 expression in peripheral CD4+ T cells demonstrated that galectin-1 is upregulated with time after stimulation, reaching high levels by 48 hours post-stimulation. Galectin-1 binding had differential effects on peripheral CD4+ Th1 and Th2 effector populations. Our results showed that galectin-1 induced apoptosis in Th1 but not Th2 cells, although galectin-1 binding levels were similar between these two populations. In contrast, galectin-1 specifically enhanced secretion of Th2-type cytokines. Differential effects of galectin-1 on activation of TCR signaling intermediates were also seen between Th1 and Th2 subsets.