Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death

Galectins are a family of mammalian beta-galactoside-binding proteins that positively and negatively regulate T cell death. Extracellular Galectin-1 directly induces death of T cells and thymocytes, while intracellular Galectin-3 blocks T cell death. In contrast to the antiapoptotic function of intracellular Galectin-3, we demonstrate that extracellular Galectin-3 directly induces death of human thymocytes and T cells. However, events in galectin-3- and galectin-1-induced cell death differ in a number of ways. Thymocyte subsets demonstrate different susceptibility to the two galectins: whereas Galectin-1 kills double-negative and double-positive human thymocytes with equal efficiency, Galectin-3 preferentially kills double-negative thymocytes. Galectin-3 binds to a complement of T cell surface glycoprotein receptors distinct from that recognized by Galectin-1. Of these glycoprotein receptors, CD45 and CD71, but not CD29 and CD43, appear to be involved in galectin-3-induced T cell death. In addition, CD7 that is required for galectin-1-induced death is not required for death triggered by Galectin-3. Following Galectin-3 binding, CD45 remains uniformly distributed on the cell surface, in contrast to the CD45 clustering induced by Galectin-1. Thus, extracellular Galectin-3 and Galectin-1 induce death of T cells through distinct cell surface events. However, as Galectin-3 and Galectin-1 cell death are neither additive nor synergistic, the two death pathways may converge inside the cell.