Background and objectives 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 the function of Gal-1 expressed by activated T-cells we have carried out a series of experiments.

Methods Activated T-cells from healthy humans, Gal-1 knock-out and wild-type mice, and Gal-1 transgenic Jurkat (J^Gal) cells, established in our laboratory, were studied. Furthermore, T-cells were isolated from SLE patients during active disease (n = 20), in remission (n = 10), and healthy controls (n = 20). The expression and localisation of Gal-1 were examined with QPCR, Western blotting, cytofluorimetry or confocal microscopy. Apoptosis was studied in co-culture of PHA-activated T-cells with Gal-1-expressing HeLa tumour cells using fluorescent microscopy.

Results Both J^Galand activated T-cells produced Gal-1. The protein remained intracellularly without secretion. Wild-type mouse and Gal-1 transgenic Jurkat T-cells were significantly more susceptible to the apoptotic effect of exGal-1 than Gal-1 deficient mouse and wild type (Gal-1 non-expressing) Jurkat T-cells. Accordingly, activated T-cells from SLE patients which produced significantly less inGal-1 than the healthy control cells or T-cells from patients in remission after successful immunosuppressive therapy, responded poorly to the apoptotic signal by exGal-1 compared to those of healthy and inactive-lupus T-cells.

Conclusions We have demonstrated in three independent experimental systems that the de novo expressed Gal-1 in activated T-cells remained intracellularly, confirming that the function of T-cell derived Gal-1 was not the regulation of T-cell viability via an autocrine fashion. Rather, the inGal-1 effectively regulated T-cell apoptosis triggered by environmental exGal-1. Moreover, we showed that low expression of Gal-1 in SLE T-cells resulted in the diminished down regulation of T-cell activity by 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.