Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2S congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes

Bernhard Greve, Jayagopala Reddy, Hans Peter Waldner, Raymond A. Sobel, Vijay K. Kuchroo

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Nonobese diabetic (NOD) mice develop multi-organ autoimmune diseases, including type 1 diabetes. We hypothesized that backcrossing the MHC region from SJL (H-2s) mice, which have an endogenous PLP139-151-reactive repertoire, onto the background of autoimmune-prone NOD mice would result in a mouse strain that is highly susceptible to experimental autoimmune encephalomyelitis (EAE). Unexpectedly, although we detected an endogenous PLP139-151 repertoire in the NOD.S mice, they did not develop spontaneous EAE and were relatively resistant to PLP139-151-induced EAE when compared to SJL mice. This resistance was associated with lower production of proinflammatory cytokines and a decreased expansion of PLP139-151-specific CD4+ T cells after immunization and restimulation with PLP peptide in vitro. Vβ chain usage among PLP139-151-reactive T cells differed between SJL and NOD.S mice. Furthermore, NODS mice were resistant to the development of insulitis and cyclophosphamide-induced diabetes, but not sialadenitis. Altogether, even though NOD. mice develop spontaneous autoimmune diseases, they become relatively resistant to induction of EAE even when they express the EAE-permissive class II molecule I-As. Our data show that certain combinations of otherwise susceptibility-conferring MHC and non-MHC genes can mediate autoimmune-disease resistance when they are paired together. These findings do not support the "shared autoimmune gene" hypothesis.

Original languageEnglish (US)
Pages (from-to)1828-1838
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number7
DOIs
StatePublished - Jul 2004

Keywords

  • Diabetes
  • EAE/MS
  • MHC
  • Rodent
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2<sup>S</sup> congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes'. Together they form a unique fingerprint.

Cite this