Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system

Prevot, Nicolas, Briet, Claire, Lassmann, Hans, Tardivel, Isabelle, Roy, Edwige, Morin, Joelle, Mak, Tak W., Tafuri, Anna and Boitard, Christian (2010) Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system. European Journal of Immunology, 40 8: 2267-2276. doi:10.1002/eji.201040416


Author Prevot, Nicolas
Briet, Claire
Lassmann, Hans
Tardivel, Isabelle
Roy, Edwige
Morin, Joelle
Mak, Tak W.
Tafuri, Anna
Boitard, Christian
Title Abrogation of ICOS/ICOS ligand costimulation in NOD mice results in autoimmune deviation toward the neuromuscular system
Journal name European Journal of Immunology   Check publisher's open access policy
ISSN 0014-2980
1521-4141
Publication date 2010-08-01
Sub-type Article (original research)
DOI 10.1002/eji.201040416
Volume 40
Issue 8
Start page 2267
End page 2276
Total pages 10
Place of publication Weinheim, Germany
Publisher Wiley - VCH Verlag
Language eng
Formatted abstract
NOD mice spontaneously develop insulin-dependent diabetes around 10–40 wk of age. Numerous immune gene variants contribute to the autoimmune process. However, genes that direct the autoimmune response toward β cells remain ill defined. In this study, we provide evidence that the Icos and Icosl genes contribute to the diabetes process. Protection from diabetes in ICOS−/− and ICOSL−/− NOD mice was unexpectedly associated with the development of an autoimmune disorder of the neuro-muscular system, characterized by myositis, sensory ganglionitis and, to a reduced extent, inflammatory infiltrates in the CNS. This syndrome was reproduced upon adoptive transfer of CD4+ and CD8+ T cells from diseased donors to naïve NOD.scid recipients. Our data further show that protection from diabetes results from defective activation of autoimmune diabetogenic effector T cells in ICOS−/− NOD mice, whereas acceleration of diabetes in BDC2.5 ICOS−/− NOD mice is induced by a dominant defect in Treg. Taken together, our findings indicate that costimulation signals play a key role in regulating immune tolerance in peripheral tissues and that the ICOS/ICOSL costimulatory pathway influences the balance between Treg and diabetogenic effector T cells.
Keyword Autoimmunity
Costimulation
ICOS
ICOS ligand
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
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Created: Sat, 22 Oct 2011, 03:56:13 EST by Edwige Roy on behalf of UQ Centre for Clinical Research