Article Text

PDF
A2.9 Novel role for galectin-1 in T-cell apoptosis regulation and ist relevance to systemic lupus erythematosus
  1. A Hornung1,2,
  2. M Deák1,
  3. J Novák2,
  4. E Szabó2,
  5. A Czibula2,
  6. R Fajka-Boja2,
  7. Kriston-Pá É1,2,
  8. Monostori É2,
  9. L Kovács1
  1. 1Department of Rheumatology, University of Szeged, Faculty of Medicine, Albert Szent-Györgyi Health Centre, Szeged, Hungary
  2. 2Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, Szeged, Hungary

Abstract

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 (JGal) 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 JGaland 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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.