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

Type 1 diabetes (T1D) is a disease caused by the destruction of the β cells of the pancreas by activated T cells. Dendritic cells (BC) 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 i...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Perone, M.J., Bertera, S., Tawadrous, Z.S., Shufesky, W.J., Piganelli, J.D., Baum, L.G., Trucco, M., Morelli, A.E.
Formato: Artículo publishedVersion
Publicado: 2006
Materias:
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00221767_v177_n8_p5278_Perone
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00221767_v177_n8_p5278_Perone_oai
Aporte de:
id I28-R145-paper_00221767_v177_n8_p5278_Perone_oai
record_format dspace
spelling I28-R145-paper_00221767_v177_n8_p5278_Perone_oai2020-10-19 Perone, M.J. Bertera, S. Tawadrous, Z.S. Shufesky, W.J. Piganelli, J.D. Baum, L.G. Trucco, M. Morelli, A.E. 2006 Type 1 diabetes (T1D) is a disease caused by the destruction of the β cells of the pancreas by activated T cells. Dendritic cells (BC) 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-γ-secreting CD4+ T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN-γ of T cells in response to β 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 β cell-reactive T cells at early stages of the disease when the diabetogenic T cells are already activated. Copyright © 2005 by The American Association of Immunologists, Inc. application/pdf http://hdl.handle.net/20.500.12110/paper_00221767_v177_n8_p5278_Perone info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar J. Immunol. 2006;177(8):5278-5289 galectin 1 gamma interferon adoptive transfer animal cell animal experiment animal model animal tissue antigen presenting cell apoptosis article autoimmune disease CD4+ T lymphocyte cellular immunity controlled study cytokine release dendritic cell disease model down regulation female GAL1 gene genetic engineering insulin dependent diabetes mellitus insulitis lymph node lymphocyte proliferation mouse nonhuman pancreas islet beta cell priority journal protein function protein synthesis spleen T lymphocyte activation Th1 cell transgene Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00221767_v177_n8_p5278_Perone_oai
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-145
collection Repositorio Digital de la Universidad de Buenos Aires (UBA)
topic galectin 1
gamma interferon
adoptive transfer
animal cell
animal experiment
animal model
animal tissue
antigen presenting cell
apoptosis
article
autoimmune disease
CD4+ T lymphocyte
cellular immunity
controlled study
cytokine release
dendritic cell
disease model
down regulation
female
GAL1 gene
genetic engineering
insulin dependent diabetes mellitus
insulitis
lymph node
lymphocyte proliferation
mouse
nonhuman
pancreas islet beta cell
priority journal
protein function
protein synthesis
spleen
T lymphocyte activation
Th1 cell
transgene
spellingShingle galectin 1
gamma interferon
adoptive transfer
animal cell
animal experiment
animal model
animal tissue
antigen presenting cell
apoptosis
article
autoimmune disease
CD4+ T lymphocyte
cellular immunity
controlled study
cytokine release
dendritic cell
disease model
down regulation
female
GAL1 gene
genetic engineering
insulin dependent diabetes mellitus
insulitis
lymph node
lymphocyte proliferation
mouse
nonhuman
pancreas islet beta cell
priority journal
protein function
protein synthesis
spleen
T lymphocyte activation
Th1 cell
transgene
Perone, M.J.
Bertera, S.
Tawadrous, Z.S.
Shufesky, W.J.
Piganelli, J.D.
Baum, L.G.
Trucco, M.
Morelli, A.E.
Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
topic_facet galectin 1
gamma interferon
adoptive transfer
animal cell
animal experiment
animal model
animal tissue
antigen presenting cell
apoptosis
article
autoimmune disease
CD4+ T lymphocyte
cellular immunity
controlled study
cytokine release
dendritic cell
disease model
down regulation
female
GAL1 gene
genetic engineering
insulin dependent diabetes mellitus
insulitis
lymph node
lymphocyte proliferation
mouse
nonhuman
pancreas islet beta cell
priority journal
protein function
protein synthesis
spleen
T lymphocyte activation
Th1 cell
transgene
description Type 1 diabetes (T1D) is a disease caused by the destruction of the β cells of the pancreas by activated T cells. Dendritic cells (BC) 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-γ-secreting CD4+ T cells in pancreatic lymph nodes. Treatment with gal-1-DC inhibited proliferation and secretion of IFN-γ of T cells in response to β 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 β cell-reactive T cells at early stages of the disease when the diabetogenic T cells are already activated. Copyright © 2005 by The American Association of Immunologists, Inc.
format Artículo
Artículo
publishedVersion
author Perone, M.J.
Bertera, S.
Tawadrous, Z.S.
Shufesky, W.J.
Piganelli, J.D.
Baum, L.G.
Trucco, M.
Morelli, A.E.
author_facet Perone, M.J.
Bertera, S.
Tawadrous, Z.S.
Shufesky, W.J.
Piganelli, J.D.
Baum, L.G.
Trucco, M.
Morelli, A.E.
author_sort Perone, M.J.
title Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_short Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_full Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_fullStr Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_full_unstemmed Dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
title_sort dendritic cells expressing transgenic galectin-1 delay onset of autoimmune diabetes in mice
publishDate 2006
url http://hdl.handle.net/20.500.12110/paper_00221767_v177_n8_p5278_Perone
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00221767_v177_n8_p5278_Perone_oai
work_keys_str_mv AT peronemj dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT berteras dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT tawadrouszs dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT shufeskywj dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT piganellijd dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT baumlg dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT truccom dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
AT morelliae dendriticcellsexpressingtransgenicgalectin1delayonsetofautoimmunediabetesinmice
_version_ 1766026586942865408