Responses against islet antigens in NOD mice are prevented by tolerance to proinsulin but not IGRP
Details
Publication Year 2006-12, Volume 116, Issue #12, Page 3258-3265
Journal Title
JOURNAL OF CLINICAL INVESTIGATION
Publication Type
Journal Article
Abstract
Type 1 diabetes (T1D) is characterized by immune responses against several autoantigens expressed in pancreatic P cells. T cells specific for proinsullin and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) can induce T1D in NOD mice. However, whether immune responses to multiple autoantigens are caused by spreading from one to another or whether they develop independently of each other is unknown. As cytotoxic T cells specific for IGRP were not detected in transgenic NOD mice tolerant to proinsulin, we determined that immune responses against proinsulin are necessary for IGRP-specific T cells to develop. On the other hand, transgenic overexpression of IGRP resulted in loss of intra-islet IGRP-specific T cells but did not protect NOD mice from insulitis or T1D, providing direct evidence that the response against IGRP is downstream of the response to proinsulin. Our results suggest that pathogenic proinsuhn-specific immunity in NOD mice subsequently spreads to other antigens such as IGRP.
Publisher
AMER SOC CLINICAL INVESTIGATION INC
Keywords
NONOBESE DIABETIC MICE; CD8(+) T-CELLS; DENDRITIC CELLS; IDENTIFICATION; AUTOANTIGEN; EPITOPE; ACCELERATION; AUTOIMMUNITY; POPULATION; EXPRESSION
Publisher's Version
https://doi.org/10.1172/JCI29602
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2006-12-01 12:00:00
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙