Secreted, extracellular galectin-1 (exGal-1) but not intracellular Gal-1 (inGal-1)
has been described as a strong immunosuppressive protein due to its major activity
of inducing apoptosis of activated T-cells. It has previously been reported that T-cells
express Gal-1 upon activation, however its participation in T-cell functions has remained
largely elusive. To determine function of Gal-1 expressed by activated T-cells we
have carried out a series of experiments. We have shown that Gal-1, expressed in Gal-1-transgenic
Jurkat cells or in activated T-cells, remained intracellularly indicating that Gal-1-induced
T-cell death was not a result of an autocrine effect of the de novo expressed Gal-1.
Rather, a particular consequence of the inGal-1 expression was that T-cells became
more sensitive to exGal-1 added either as a soluble protein or bound to the surface
of a Gal-1-secreting effector cell. This was also verified when the susceptibility
of activated T-cells from wild type or Gal-1 knockout mice to Gal-1-induced apoptosis
were compared. Murine T-cells expressing Gal-1 were more sensitive to the cytotoxicity
of the exGal-1 than their Gal-1 knockout counterparts. We also conducted a study with
activated T-cells from patients with systemic lupus erythematosus (SLE), a disease
in which dysregulated T-cell apoptosis has been well described. SLE T-cells expressed
lower amounts of Gal-1 than healthy T-cells and were less sensitive to exGal-1. These
results suggested a novel role of inGal-1 in T-cells as a regulator of T-cell response
to exGal-1, and its likely contribution to the mechanism in T-cell apoptosis deficiency
in lupus.
