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APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development

BACKGROUND: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4(+)CD25(+) regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4(+)CD25(+) regu...

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Autores principales: Manirarora, Jean N., Kosiewicz, Michele M., Parnell, Sarah A., Alard, Pascale
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2580026/
https://www.ncbi.nlm.nih.gov/pubmed/19011680
http://dx.doi.org/10.1371/journal.pone.0003739
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author Manirarora, Jean N.
Kosiewicz, Michele M.
Parnell, Sarah A.
Alard, Pascale
author_facet Manirarora, Jean N.
Kosiewicz, Michele M.
Parnell, Sarah A.
Alard, Pascale
author_sort Manirarora, Jean N.
collection PubMed
description BACKGROUND: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4(+)CD25(+) regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4(+)CD25(+) regulatory cells in vivo could compromise their ability to control pathogenic cells, and activation of NOD APC could restore this defect, thereby preventing disease. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, we used the well-documented ability of complete Freund's adjuvant (CFA), an APC activator, to prevent disease in NOD mice. Phenotype and function of CD4(+)CD25(+) regulatory cells from untreated and CFA-treated NOD mice were determined by FACS, and in vitro and in vivo assays. APC from these mice were also evaluated for their ability to activate regulatory cells in vitro. We have found that sick NOD CD4(+)CD25(+) cells expressed Foxp3 at the same percentages, but decreased levels per cell, compared to young NOD or non-NOD controls. Treatment with CFA increased Foxp3 expression in NOD cells, and also increased the percentages of CD4(+)CD25(+)Foxp3(+) cells infiltrating the pancreas compared to untreated NOD mice. Moreover, CD4(+)CD25(+) cells from pancreatic LN of CFA-treated, but not untreated, NOD mice transferred protection from diabetes. Finally, APC isolated from CFA-treated mice increased Foxp3 and granzyme B expression as well as regulatory function by NOD CD4(+)CD25(+) cells in vitro compared to APC from untreated NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that regulatory T cell function and ability to control pathogenic cells can be enhanced in NOD mice by activating NOD APC.
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spelling pubmed-25800262008-11-17 APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development Manirarora, Jean N. Kosiewicz, Michele M. Parnell, Sarah A. Alard, Pascale PLoS One Research Article BACKGROUND: Defects in APC and regulatory cells are associated with diabetes development in NOD mice. We have shown previously that NOD APC are not effective at stimulating CD4(+)CD25(+) regulatory cell function in vitro. We hypothesize that failure of NOD APC to properly activate CD4(+)CD25(+) regulatory cells in vivo could compromise their ability to control pathogenic cells, and activation of NOD APC could restore this defect, thereby preventing disease. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, we used the well-documented ability of complete Freund's adjuvant (CFA), an APC activator, to prevent disease in NOD mice. Phenotype and function of CD4(+)CD25(+) regulatory cells from untreated and CFA-treated NOD mice were determined by FACS, and in vitro and in vivo assays. APC from these mice were also evaluated for their ability to activate regulatory cells in vitro. We have found that sick NOD CD4(+)CD25(+) cells expressed Foxp3 at the same percentages, but decreased levels per cell, compared to young NOD or non-NOD controls. Treatment with CFA increased Foxp3 expression in NOD cells, and also increased the percentages of CD4(+)CD25(+)Foxp3(+) cells infiltrating the pancreas compared to untreated NOD mice. Moreover, CD4(+)CD25(+) cells from pancreatic LN of CFA-treated, but not untreated, NOD mice transferred protection from diabetes. Finally, APC isolated from CFA-treated mice increased Foxp3 and granzyme B expression as well as regulatory function by NOD CD4(+)CD25(+) cells in vitro compared to APC from untreated NOD mice. CONCLUSIONS/SIGNIFICANCE: These data suggest that regulatory T cell function and ability to control pathogenic cells can be enhanced in NOD mice by activating NOD APC. Public Library of Science 2008-11-17 /pmc/articles/PMC2580026/ /pubmed/19011680 http://dx.doi.org/10.1371/journal.pone.0003739 Text en Manirarora et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Manirarora, Jean N.
Kosiewicz, Michele M.
Parnell, Sarah A.
Alard, Pascale
APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development
title APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development
title_full APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development
title_fullStr APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development
title_full_unstemmed APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development
title_short APC Activation Restores Functional CD4(+)CD25(+) Regulatory T Cells in NOD Mice that Can Prevent Diabetes Development
title_sort apc activation restores functional cd4(+)cd25(+) regulatory t cells in nod mice that can prevent diabetes development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2580026/
https://www.ncbi.nlm.nih.gov/pubmed/19011680
http://dx.doi.org/10.1371/journal.pone.0003739
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