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Influence on spontaneous tissue inflammation by the major histocompatibility complex region in the nonobese diabetic mouse.

Lindqvist, Anna-Karin LU ; Nakken, B; Sundler, M; Kjellén, P; Jonsson, R; Holmdahl, Rikard LU and Skarstein, K (2005) In Scandinavian Journal of Immunology 61(2). p.119-127
Abstract
We investigated the role of the major histocompatibility complex (MHC) region in the specificity of autoimmunity by analysing specifically the development of sialadenitis, but also insulitis, nephritis and autoantibody production in autoimmune-prone nonobese diabetic (NOD) mice where the MHC H2g7 haplotype had been exchanged for the H2q (NOD.Q) or H2p (NOD.P) haplotype. The exchange of H2 haplotype did not affect the frequency of sialadenitis because the H2q and H2p congenic NOD strains developed sialadenitis with the same incidence as NOD. However, the severity of sialadenitis varied among the strains, as NOD.Q > NOD > NOD.P. At 11–13 weeks of age, the NOD.Q (H2q) female mice developed more severe sialadenitis compared to NOD.P... (More)
We investigated the role of the major histocompatibility complex (MHC) region in the specificity of autoimmunity by analysing specifically the development of sialadenitis, but also insulitis, nephritis and autoantibody production in autoimmune-prone nonobese diabetic (NOD) mice where the MHC H2g7 haplotype had been exchanged for the H2q (NOD.Q) or H2p (NOD.P) haplotype. The exchange of H2 haplotype did not affect the frequency of sialadenitis because the H2q and H2p congenic NOD strains developed sialadenitis with the same incidence as NOD. However, the severity of sialadenitis varied among the strains, as NOD.Q > NOD > NOD.P. At 11–13 weeks of age, the NOD.Q (H2q) female mice developed more severe sialadenitis compared to NOD.P (H2p) (P = 0.038). At 20 weeks, the NOD (H2g7) female mice showed more severe sialadenitis than NOD.P (P = 0.049). This is in contrast to the development of insulitis in the present strains, because the incidence of insulitis was almost completely inhibited by the replacement of the H2g7 haplotype of NOD. The incidence of insulitis in NOD.Q was 11–22%, compared to 75% in NOD, which correlated well with lower titres of anti-glutamic acid decarboxylase (anti-GAD) antibodies in NOD.Q compared to NOD (P = 0.009). However, the introduction of the H2q haplotype into the NOD strain instead directed the autoimmune response towards the production of lupus types of autoantibodies, because the incidence of antinuclear antibodies (ANA) in NOD.Q was 89% compared with 11% in NOD.P and 12% in NOD mice, which in turn correlated with a high incidence of nephritis in NOD.Q compared to NOD. Consequently, we show that different haplotypes of MHC are instrumental in directing the specificity of the spontaneous autoimmune inflammation.

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published
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Scandinavian Journal of Immunology
volume
61
issue
2
pages
119 - 127
publisher
Wiley-Blackwell
external identifiers
  • wos:000226708100002
  • pmid:15683448
  • scopus:13844271553
ISSN
1365-3083
DOI
10.1111/j.0300-9475.2005.01550.x
language
English
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yes
id
912a7495-9283-4a04-865b-770ccc5cdd18 (old id 133971)
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2007-07-17 08:11:40
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@article{912a7495-9283-4a04-865b-770ccc5cdd18,
  abstract     = {We investigated the role of the major histocompatibility complex (MHC) region in the specificity of autoimmunity by analysing specifically the development of sialadenitis, but also insulitis, nephritis and autoantibody production in autoimmune-prone nonobese diabetic (NOD) mice where the MHC H2g7 haplotype had been exchanged for the H2q (NOD.Q) or H2p (NOD.P) haplotype. The exchange of H2 haplotype did not affect the frequency of sialadenitis because the H2q and H2p congenic NOD strains developed sialadenitis with the same incidence as NOD. However, the severity of sialadenitis varied among the strains, as NOD.Q &gt; NOD &gt; NOD.P. At 11–13 weeks of age, the NOD.Q (H2q) female mice developed more severe sialadenitis compared to NOD.P (H2p) (P = 0.038). At 20 weeks, the NOD (H2g7) female mice showed more severe sialadenitis than NOD.P (P = 0.049). This is in contrast to the development of insulitis in the present strains, because the incidence of insulitis was almost completely inhibited by the replacement of the H2g7 haplotype of NOD. The incidence of insulitis in NOD.Q was 11–22%, compared to 75% in NOD, which correlated well with lower titres of anti-glutamic acid decarboxylase (anti-GAD) antibodies in NOD.Q compared to NOD (P = 0.009). However, the introduction of the H2q haplotype into the NOD strain instead directed the autoimmune response towards the production of lupus types of autoantibodies, because the incidence of antinuclear antibodies (ANA) in NOD.Q was 89% compared with 11% in NOD.P and 12% in NOD mice, which in turn correlated with a high incidence of nephritis in NOD.Q compared to NOD. Consequently, we show that different haplotypes of MHC are instrumental in directing the specificity of the spontaneous autoimmune inflammation.<br/><br>
This article is cited by:},
  author       = {Lindqvist, Anna-Karin and Nakken, B and Sundler, M and Kjellén, P and Jonsson, R and Holmdahl, Rikard and Skarstein, K},
  issn         = {1365-3083},
  language     = {eng},
  number       = {2},
  pages        = {119--127},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Influence on spontaneous tissue inflammation by the major histocompatibility complex region in the nonobese diabetic mouse.},
  url          = {http://dx.doi.org/10.1111/j.0300-9475.2005.01550.x},
  volume       = {61},
  year         = {2005},
}