Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis butinhibit IL-2 production and proliferation

Galectin-1 is an endogenous lectin expressed by thymic and lymph node strom al cells at sites of Ag presentation and T cell death during normal develop ment. It is known to have immunomodulatory activity in vivo and can induce apoptosis in thymocytes and activated T cells (1-3), Here we demonstrate th at galectin-1 stimulation cooperates with TCR engagement to induce apoptosi s, but antagonizes TCR-induced IL-2 production and proliferation in a murin e T cell hybridoma and freshly isolated mouse thymocytes, respectively. Alt hough CD4(+)CD8(+) double positive cells are the primary thymic subpopulati on susceptible to galectin-1 treatment alone, concomitant CD3 engagement an d galectin-1 stimulation broaden susceptible thymocyte subpopulations to in clude a subset of each CD4(-)CD8(-), CD4(+)CD8(+), CD4(-)CD8(+), and CD4(+) CD8(-) subpopulations. Furthermore, CD3 engagement cooperates with suboptim al galectin-1 stimulation to enhance cell death in the CD4+CD8+ subpopulati on. Galectin-1 stimulation is shown to synergize with TCR engagement to dra matically and specifically enhance extracellular signal-regulated kinase-2 (ERK-2) activation, though it does not uniformly enhance TCR-induced tyrosi ne phosphorylation, Unlike TCR-induced IL-2 production, TCR/galectin-1-indu ced apoptosis is not modulated by the expression of kinase inactive or cons titutively activated Lck, These data support a role for galectin-1 as a pot ent modulator of TCR signals and functions and indicate that individual TCR -induced signals can be independently modulated to specifically affect dist inct TCR functions.