Interferon-gamma plays a role in pancreatic islet-cell destruction of reovirus type 2-induced diabetes-like syndrome in DBA/1 suckling mice.
Reovirus type 2 (Reo-2) infection in DBA/1 suckling mice causes insulitis, which leads to pancreatic islet-cell destruction, resulting in a diabetes-like syndrome. T-helper (Th) 1 cytokines are thought to play a key role in islet inflammation in insulin-dependent diabetes mellitus. We examined this hypothesis in the Reo-2-induced diabetes-like syndrome. We used reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR techniques to examine mRNA expression of interferon (IFN)-gamma (Th1 type cytokine), and interleukin (IL)-4 (Th2 type cytokine) in splenic cells. We observed that in Reo-2 infected mice the level of IFN-gamma expression increases with the development of insulitis, whereas expression of message for IL-4 is minimal to detectable with the immuno-inflammatory process 10 days after infection. The treatment of monoclonal antibody (mAb) against mouse IFN-gamma during the expansion phase of insulitis (5-9 days after infection) inhibited the development of insulitis and the elevation of blood glucose concentrations in a dose dependent manner. Furthermore altered CD4+/CD8+ cell ratio compared with uninfected mice in the splenic cells by the infection was recovered to the ratio of uninfected mice by the treatment of mAb against mouse IFN-gamma, suggesting normalization of T cell balance in immune system. These results suggest that Reo-2-triggered autoimmune insulitis may be mediated by Th1 lymphocytes and IFN-gamma may play a role in islet inflammation leading to islet cell destruction.
Hayashi
T
T
Laboratory of Veterinary Pathology, Yamaguchi University, Japan.
Morimoto
M
M
Iwata
H
H
Onodera
T
T
D000818:Animals; D000833:Animals, Suckling; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016516:CD4-CD8 Ratio; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018165:Orthoreovirus; D012333:RNA, Messenger / Q000235:genetics; D012088:Reoviridae Infections / Q000150:complications*; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma