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Citations to this article

Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells
Hélène Bour-Jordan, … , Matthew R. Bernhard, Jeffrey A. Bluestone
Hélène Bour-Jordan, … , Matthew R. Bernhard, Jeffrey A. Bluestone
Published October 1, 2004
Citation Information: J Clin Invest. 2004;114(7):979-987. https://doi.org/10.1172/JCI20483.
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Article Autoimmunity

Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells

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Abstract

The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse results from a breakdown in tolerance to pancreatic islet antigens. CD28-B7 and CD40 ligand–CD40 (CD40L-CD40) costimulatory pathways affect the development of disease and are promising therapeutic targets. Indeed, it was shown previously that diabetes fails to develop in NOD–B7-2–/– and NOD-CD40L–/– mice. In this study, we examined the relative role of these 2 costimulatory pathways in the balance of autoimmunity versus regulation in NOD mice. We demonstrate that initiation but not effector function of autoreactive T cells was defective in NOD–B7-2–/– mice. Moreover, the residual proliferation of the autoreactive cells was effectively controlled by CD28-dependent CD4+CD25+ regulatory T cells (Treg’s), as depletion of Treg’s partially restored proliferation of autoreactive T cells and resulted in diabetes in an adoptive-transfer model. Similarly, disruption of the CD28-B7 pathway and subsequent Treg deletion restored autoimmunity in NOD-CD40L–/– mice. These results demonstrate that development of diabetes is dependent on a balance of pathogenic and regulatory T cells that is controlled by costimulatory signals. Thus, elimination of Treg’s results in diabetes even in the absence of costimulation, which suggests a need for alternative strategies for immunotherapeutic approaches.

Authors

Hélène Bour-Jordan, Benoît L. Salomon, Heather L. Thompson, Gregory L. Szot, Matthew R. Bernhard, Jeffrey A. Bluestone

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Total citations by year

Year: 2024 2022 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Total
Citations: 3 1 1 4 7 4 5 1 3 5 3 5 8 8 8 3 4 73
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