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.
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-gamma (IFN-gamma) and decreased that of interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) 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.
Laboratory of Veterinary Pathology, Yamaguchi University, Yoshida, Yamaguchi, Japan. hayasi@yamaguchi-u.ac.jp
T
T
Hayashi
K
K
Hasegawa
Y
Y
Sasaki
T
T
Onodera
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000821:virology; D005260:Female; D005951:Glucose Tolerance Test; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009841:Oligonucleotides / Q000276:immunology; D030102:Orthoreovirus, Mammalian / Q000276:immunology*; D010179:Pancreas / Q000276:immunology / Q000821:virology; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D012088:Reoviridae Infections / Q000150:complications / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000821:virology
D000911:Antibodies, Monoclonal; D000956:Antigens, Viral; D001786:Blood Glucose; D016207:Cytokines; D009841:Oligonucleotides; D015375:Receptors, Interleukin-2