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Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2(s) congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes.
Eur J Immunol. 2004 Jul; 34(7):1828-38.EJ

Abstract

Nonobese diabetic (NOD) mice develop multi-organ autoimmune diseases, including type 1 diabetes. We hypothesized that backcrossing the MHC region from SJL (H-2(s)) mice, which have an endogenous PLP(139-151)-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 PLP(139-151) repertoire in the NOD.S mice, they did not develop spontaneous EAE and were relatively resistant to PLP(139-151)-induced EAE when compared to SJL mice. This resistance was associated with lower production of proinflammatory cytokines and a decreased expansion of PLP(139-151)-specific CD4(+) T cells after immunization and restimulation with PLP peptide in vitro. V(beta) chain usage among PLP(139-151)-reactive T cells differed between SJL and NOD.S mice. Furthermore, NOD.S 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-A(s). 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.

Authors+Show Affiliations

Center for Neurologic Diseases, Harvard Institutes of Medicine, Brigham and Women's Hospital, Boston, MA 02120, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15214031

Citation

Greve, Bernhard, et al. "Dissimilar Background Genes Control Susceptibility to Autoimmune Disease in the Context of Different MHC Haplotypes: NOD.H-2(s) Congenic Mice Are Relatively Resistant to Both Experimental Autoimmune Encephalomyelitis and Type I Diabetes." European Journal of Immunology, vol. 34, no. 7, 2004, pp. 1828-38.
Greve B, Reddy J, Waldner HP, et al. Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2(s) congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes. Eur J Immunol. 2004;34(7):1828-38.
Greve, B., Reddy, J., Waldner, H. P., Sobel, R. A., & Kuchroo, V. K. (2004). Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2(s) congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes. European Journal of Immunology, 34(7), 1828-38.
Greve B, et al. Dissimilar Background Genes Control Susceptibility to Autoimmune Disease in the Context of Different MHC Haplotypes: NOD.H-2(s) Congenic Mice Are Relatively Resistant to Both Experimental Autoimmune Encephalomyelitis and Type I Diabetes. Eur J Immunol. 2004;34(7):1828-38. PubMed PMID: 15214031.
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TY - JOUR T1 - Dissimilar background genes control susceptibility to autoimmune disease in the context of different MHC haplotypes: NOD.H-2(s) congenic mice are relatively resistant to both experimental autoimmune encephalomyelitis and type I diabetes. AU - Greve,Bernhard, AU - Reddy,Jayagopala, AU - Waldner,Hans-Peter, AU - Sobel,Raymond A, AU - Kuchroo,Vijay K, PY - 2004/6/24/pubmed PY - 2004/8/11/medline PY - 2004/6/24/entrez SP - 1828 EP - 38 JF - European journal of immunology JO - Eur. J. Immunol. VL - 34 IS - 7 N2 - Nonobese diabetic (NOD) mice develop multi-organ autoimmune diseases, including type 1 diabetes. We hypothesized that backcrossing the MHC region from SJL (H-2(s)) mice, which have an endogenous PLP(139-151)-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 PLP(139-151) repertoire in the NOD.S mice, they did not develop spontaneous EAE and were relatively resistant to PLP(139-151)-induced EAE when compared to SJL mice. This resistance was associated with lower production of proinflammatory cytokines and a decreased expansion of PLP(139-151)-specific CD4(+) T cells after immunization and restimulation with PLP peptide in vitro. V(beta) chain usage among PLP(139-151)-reactive T cells differed between SJL and NOD.S mice. Furthermore, NOD.S 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-A(s). 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. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/15214031/Dissimilar_background_genes_control_susceptibility_to_autoimmune_disease_in_the_context_of_different_MHC_haplotypes:_NOD_H_2_s__congenic_mice_are_relatively_resistant_to_both_experimental_autoimmune_encephalomyelitis_and_type_I_diabetes_ L2 - https://doi.org/10.1002/eji.200425116 DB - PRIME DP - Unbound Medicine ER -