Induction of T Lymphocyte Apoptosis: A Novel Function for Galectin-1

Abstract

Galectin-1, a member of the galectin family of β-galactoside binding proteins, is produced by many types of normal and neoplastic cells. Galectin-1 has been proposed to have a variety of functions, such as mediating cell-cell interactions and influencing cell growth.
Recently, we have identified a possible additional function for galectin-1 as a mediator of T cell apoptosis, or physiologic cell death. Apoptosis is a crucial mechanism for the production of immunocompetent T cells in thymus and for the termination of an immune response in peripheral lymphoid organs. In the immune system, galectin-1 is expressed in human thymus, lymph node, and spleen. The presence of galectin-1 within lymphoid organs, and the ability of galectin-1 to induce apoptosis of thymocytes and activated T cells suggests galectin-1 may play an important role in maintaining central and peripheral immune tolerance to self antigens.
Susceptibility of T cells to galectin-1 may be modulated by regulating the expression of cell surface glycoprotein counter-receptors for galectin-1. CD45, a cell surface glycoprotein counter-receptor for galectin-1, appears to be essential for triggering galectin-1 induced apoptosis. However, T cell susceptibility to galectin-1 may be further modulated by the glycosylation state of CD45, or by the presence of other galectin-1 counter-receptors, such as CD43.
Galectin-1 may also play a role in regulating the immune system in nonlymphoid organs. Galectin-1 is expressed in many immune privileged sites and tissues, such as placenta, prostate, and cornea. An immune privileged site or tissue is a region of the body where the immune response is tempered in order to protect critical organs, such as the cornea, from damage induced by the inflammatory response of activated T cells. Apoptosis has been shown to be an important mechanism for preserving immune privilege. Expression of galectin-1 in immune privileged tissues may contribute to the maintenance of immune privilege by inducing apoptosis of infiltrating activated T cells. We hypothesize that the expression of galectin-1 in lymphoid organs and in immune privileged sites may play a significant role in modulating the immune response.