Induction of allogenic T-cell hyporesponsiveness by galectin-1-mediated apoptotic and non-apoptotic mechanisms

• Published in: Cell death and differentiation Vol. 9; no. 6; pp. 661 - 670
• Main Authors: Rabinovich, G A, Ramhorst, R E, Rubinstein, N, Corigliano, A, Daroqui, M C, Kier-Joffe, E B, Fainboim, L
• Format: Journal Article
• Language: English
• Published: 01-06-2002
• ISSN: 1350-9047
• DOI: 10.1038/sj/cdd/4401009

Galectin-1, a beta -galactoside-binding protein expressed at sites of T-cell activation and immune privilege, has shown specific immunosuppressive properties. Because of the implications of this protein in T-cell tolerance and its potential use to avoid graft rejection, we investigated the immunosuppressive effects of galectin-1 in the course of the human allogenic T-cell response. Galectin-1 induced a dose- and carbohydrate-dependent inhibition of the allogenic T-cell response. Addition of galectin-1 to alloreactive lymphocytes resulted in significant apoptosis of CD45R0-positive cells. This negative regulatory effect was accompanied by caspase activation, Bcl-2 downregulation and was prevented by addition of exogenous IL-2. In addition, a significant decrease of IFN- gamma production was detected in the non-apoptotic cell population, following exposure of alloreactive lymphocytes to galectin-1. Moreover, the immunosuppressive activity of this protein did not involve TGF- beta -mediated mechanisms. Since galectin-1 is expressed by activated T cells and could be acting by an autocrine negative loop to control human T-cell reactivity, we finally examined the regulated expression of this protein throughout the allogenic T-cell response. Expression of endogenous galectin-1 was detected at 24 h of cell culture, reaching its maximal levels after 72 h of allostimulation. The present study sets the basis for a potential use of galectin-1 as a selective immunosuppressive agent to limit T-cell-mediated reactivity during the effector phase of the alloimmune response.