Induction of allogeneic T-cell hyporesponsiveness by Galectin-1-mediated apoptotic and non-apoptotic mechanisms.

G*. RABINOVICH*, R. RAMHORST*, A. CORIGLIANO, C. DAROQUI, N. RUBISTEIN, E. BAL DE KIER AND L. FAINBOIM. *R. RAMHORST Y *G. RABINOVICH COMPARTEN LA PRIMERA AUTORÍA

CELL DEATH AND DIFFERENTIATION

Nature Publishing Group

Lugar: London; Año: 2002 vol. 9 p. 661 - 670

1350-9047

Galectin-1, a -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- 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--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.