Transforming growth factor-beta inhibits coxsackievirus-mediated autoimmune myocarditis.

Clinical myocarditis is a precursor to dilated cardiomyopathy and a principal cause of heart failure. Nearly 30% of all recently diagnosed cases of myocarditis are attributable to infection with coxsackie B virus (CBV), the most frequently associated pathogen. CBV initially replicates in the pancreas and quickly spreads to the heart, inducing chronic autoimmunity.

Induction of antigen specific peripheral humoral tolerance to cardiac myosin does not prevent CB3-mediated autoimmune myocarditis.

Chronic myocarditis often progresses to dilated cardiomyopathy resulting in heart failure or cardiac transplantation. Viral infection is the most common cause of myocarditis and coxsackie B viruses (CBV) are the most frequently cited etiologic agents associated with myocarditis and cardiomyopathy. Additionally, CBV infections of genetically susceptible mice induce autoimmune myocarditis resembling human disease, including the development of autoantibodies to cardiac myosin.

Homeostatic expansion of T cells during immune insufficiency generates autoimmunity.

During illness and stress, the immune system can suffer a considerable loss of T cells (lymphopenia). The remaining T cells undergo vigorous compensatory expansion, known as homeostatic proliferation, to reconstitute the immune system. Interestingly, human diseases of autoimmune etiology often present with immune deficiencies such as lymphopenia.

Coxsackieviral-mediated diabetes: induction requires antigen-presenting cells and is accompanied by phagocytosis of beta cells.

Epidemiological studies have associated coxsackie B virus (CBV) with the development of insulin-dependent diabetes mellitus (IDDM) in humans. Infections of genetically susceptible mice with CBV strain 4 (CB4) induce autoimmune diabetes. Herein, we demonstrate that in mice, CB4 infection of insulin-producing pancreatic beta cells does not directly cause beta cell death.

Coxsackievirus-mediated hyperglycemia is enhanced by reinfection and this occurs independent of T cells.

The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longer detectable.

Presented antigen from damaged pancreatic beta cells activates autoreactive T cells in virus-mediated autoimmune diabetes.

The induction of autoimmunity by viruses has been attributed to numerous mechanisms. In mice, coxsackievirus B4 (CB4) induces insulin-dependent diabetes mellitus (IDDM) resembling the final step of disease progression in humans. The immune response following the viral insult clearly precipitates IDDM.