Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice

PERONE, M. J.; BERTERA, S.; TAWADROUS, Z. S.; SHUFESKY, W. J.; PIGANELLI, J. D.; BAUM, L. G.; TRUCCO, M.; MORELLI, A. E.

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Amer Assoc Immunologist; Año: 2006 p. 5278 - 5289

0022-1767

Abstract Type 1 diabetes (T1D) is a disease caused by the destruction of the
cells of the pancreas by activated T cells. Dendritic cells (DC) are the APC that initiate the T cell response that triggers T1D. However, DC also participate in T cell tolerance, and genetic engineering of DC to modulate T cell immunity is an area of active research. Galectin-1 (gal-1) is an endogenous lectin with regulatory effects on activated T cells including induction of apoptosis and down-regulation of the Th1 response, characteristics that make gal-1 an ideal transgene to transduce DC to treat T1D. We engineered bone marrow-derived DC to synthesize transgenic gal-1 (gal-1-DC) and tested their potential to prevent T1D through their regulatory effects on activated T cells. NOD-derived gal-1-DC triggered rapid apoptosis of diabetogenic BDC2.5 TCR-transgenic CD4 T cells by TCR-dependent and -independent mechanisms. Intravenously administered gal-1-DC trafficked to pancreatic lymph nodes and spleen and delayed onset of diabetes and insulitis in the NODrag1/ lymphocyte adoptive transfer model. The therapeutic effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells and reduced number of IFN--secreting CD4 T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN- of T cells in response to
cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to deleterag1
cells of the pancreas by activated T cells. Dendritic cells (DC) are the APC that initiate the T cell response that triggers T1D. However, DC also participate in T cell tolerance, and genetic engineering of DC to modulate T cell immunity is an area of active research. Galectin-1 (gal-1) is an endogenous lectin with regulatory effects on activated T cells including induction of apoptosis and down-regulation of the Th1 response, characteristics that make gal-1 an ideal transgene to transduce DC to treat T1D. We engineered bone marrow-derived DC to synthesize transgenic gal-1 (gal-1-DC) and tested their potential to prevent T1D through their regulatory effects on activated T cells. NOD-derived gal-1-DC triggered rapid apoptosis of diabetogenic BDC2.5 TCR-transgenic CD4 T cells by TCR-dependent and -independent mechanisms. Intravenously administered gal-1-DC trafficked to pancreatic lymph nodes and spleen and delayed onset of diabetes and insulitis in the NODrag1/ lymphocyte adoptive transfer model. The therapeutic effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells and reduced number of IFN--secreting CD4 T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN- of T cells in response to
cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to deleterag1 T cells by TCR-dependent and -independent mechanisms. Intravenously administered gal-1-DC trafficked to pancreatic lymph nodes and spleen and delayed onset of diabetes and insulitis in the NODrag1/ lymphocyte adoptive transfer model. The therapeutic effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells and reduced number of IFN--secreting CD4 T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN- of T cells in response to
cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to deleterag1/ lymphocyte adoptive transfer model. The therapeutic effect of gal-1-DC was accompanied by increased percentage of apoptotic T cells and reduced number of IFN--secreting CD4 T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN- of T cells in response to
cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to delete-secreting CD4 T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN- of T cells in response to
cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to delete of T cells in response to
cell Ag. Unlike other DC-based approaches to modulate T cell immunity, the use of the regulatory properties of gal-1-DC on activated T cells might help to delete
cell-reactive T cells at early stages of the disease when the diabetogenic T cells are already activated. The Journal of Immunology, 2006, 177: 5278–5289.cell-reactive T cells at early stages of the disease when the diabetogenic T cells are already activated. The Journal of Immunology, 2006, 177: 5278–5289.