T cells are hyperactive, aberrant, or both in lupus. Sle3 is a lupus susceptibility locus on murine chromosome 7 that is associated with spontaneous immune T cell hyperactivity and autoreactivity when placed into B6 mice with normal genetic backgrounds. In a study appearing online on June 9 in advance of the print publication of the July 1 print issue of the Journal of Clinical Investigation, Chandra Mohan and colleagues from UT Southwestern Medical school analyze the means by which Sle3 affects the phenotype of the B6.Sle3 congenics in which there is T cell hyperactivity, elevated CD4:CD8 ratios, and anti-nuclear antibodies.
The researchers demonstrate that these B6.Sle3 congenic mice exhibit heightened T cell expansion in vitro upon antigen challenge, mediated by hyperstimulated antigen presenting cells. The congenic-derived dendritic cells (DC) and macrophages are more mature/activated, and induce superior co-stimulation to T cells in vitro compared to controls. Finally, adoptive transfer of B6.Sle3-derived DCs into B6 increases the ratio of CD4:CD8 and serum anti-nuclear antibodies. That Sle3 causes aberrant activation of antigen-presenting cells is a novel observation that, and this trigger might account for the hyperactivity of T cells and break in self-tolerance seen in lupus. This new information has important implications towards our understanding of autoimmune disease, and how to manage it clinically.
Title: Genetic dissection of lupus: T-cell hyperactivity as a consequence of hyperstimulatory antigen presenting cells
AUTHOR CONTACT:
Chandra Mohan
UT Southwestern Medical Center, Dallas, TX USA
Phone: 214 648 9675; Fax: 214 648 7995; E-mail: chandra.mohan@utsouthwestern.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=23049
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Contact: Stacie Bloom
press_releases@the-jci.org
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Journal of Clinical Investigation
9-Jun-2005