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Elimination of CD4 + CD25 + Regulatory T cells Breaks Down Reovirus Type 2‐Triggered and CpG ODN‐Induced Prolonged Mild Autoimmune Insulitis in DBA/1 Mice
Author(s) -
Hayashi T.,
Hasegawa K.,
Sasaki Y.,
Onodera T.
Publication year - 2006
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2005.01717.x
Subject(s) - insulitis , cpg oligodeoxynucleotide , immunology , il 2 receptor , nod mice , type 1 diabetes , autoantibody , subclinical infection , autoimmune disease , medicine , biology , antibody , endocrinology , t cell , diabetes mellitus , immune system , biochemistry , gene expression , dna methylation , gene
We have reported previously that subclinical prolonged mild T helper (Th) 1‐dependent autoimmune insulitis with impaired glucose tolerance in wealing DBA/1J mice, which is induced by the combined effects of reovirus type 2 (Reo‐2) and synthetic 20‐base oligodeoxynucleotides with CpG motifs (CpG ODN) (control mice). Compared with the control mice, newborn mice treated with monoclonal antibody (MoAb) against mouse CD25 + CD4 + T cells together with Reo‐2 and CpG ODN greatly reduced the absolute number of splenic CD25 + T cells and resulted in the development of severe insulitis, leading to an overt early diabetes. Moreover, the treatment of the MoAb increased production of interferon‐γ (IFN‐γ) and decreased that of interleukin‐4 (IL‐4) and transforming growth factor‐β1 (TGF‐β1) and developed high titre of autoantibodies against pancreatic islet cells. These evidences suggest that CD4 + CD25 + T cell may, at least in part, maintain tolerance to Reo‐2‐triggered and CpG ODN‐induced prolonged mild Th1‐dependent autoimmune insulitis, leading to the overt disease. This system may give a novel model to elucidate the mechanisms of the development of overt diabetes from borderline subclinical diabetes in virus‐triggered autoimmune type I diabetes in human.