Cardiac Myosin and the TH1/TH2 Paradigm in Autoimmune Myocarditis

Cunningham, Madeleine W.

doi:10.1016/s0002-9440(10)61665-3

Cited by 54 publications

(47 citation statements)

References 101 publications

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“…Anti cardiac-myosin antibodies to cardiac-myosin have been reported in myocarditis patients [22,23]. Thus the present data suggest a role of T and B cell in pathogenesis of myocarditis, which is in agreement with previous findings [12,24,25]. T cell response to myosin peptide 735-747 suggests that autoreactive T cells restricted by DQ8 mediate the response to cardiac myosin in our model although the present data does not exclude the role of other peptides.…”

Section: Discussionsupporting

confidence: 91%

Spontaneous myocarditis mimicking human disease occurs in the presence of an appropriate MHC and non-MHC background in transgenic mice

Taneja

Behrens

Cooper

et al. 2007

Journal of Molecular and Cellular Cardiology

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Most individuals have viral infections at some point in their life, however, only few develop autoreactivity to cardiac myosin following infection resulting in myocarditis suggesting a genetic predisposition. Most mouse models of myocarditis are induced by viral infection or by immunization with cardiac myosin. We generated HLA-DR3.Aβo and HLA-DQ8.Aβo transgenic mice in NOD and HLA-DQ8.Aβo in B10 background to study spontaneous autoimmunity. A high mortality was observed in NOD.DQ8 female mice 16 weeks or older. Echocardiography showed marked systolic dysfunction. Histopathology of various organs revealed an enlarged heart with mononuclear infiltrate consisting of CD4 and Mac-1+ cells and myocyte necrosis. The autoimmunity was associated with the presence of spontaneous autoreactive T cells and antibodies to cardiac myosin. Serologically, mice were negative for all known mouse viruses. NOD.DR3.Aβo, the transgene negative littermates, NOD, and B10.DQ8 Aβo mice had no gross or microscopic cardiac pathology. Spontaneous cellular and humoral response to cardiac myosin suggest that NOD.DQ8 may harbor autoreative cells that can lead to spontaneous myocarditis and dilated cardiomyopathy. HLA-DQ8 is required for predisposition to the spontaneous autoreactivity while NOD background influences onset and progression of disease. This model of myocarditis occurs predominantly in female mice and may provide insight into the pathogenesis of heart disease in women.

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Section: Discussionsupporting

confidence: 91%

Spontaneous myocarditis mimicking human disease occurs in the presence of an appropriate MHC and non-MHC background in transgenic mice

Taneja

Behrens

Cooper

et al. 2007

Journal of Molecular and Cellular Cardiology

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“…Initially, it was proposed that EAM was characterized by a Th1 type response, as studies administering recombinant IL-12 into rats in vivo exacerbated EAM [27]. However, recent publications have demonstrated that the development of EAM is far more complex than previously reported [28]. IL-12p40-deficient and IL-12Rb1-deficient mice were shown to be protected against EAM, while IFN-c-or IFN-c R-deficient mice demonstrated greatly exacerbated disease [29,30].…”

Section: Introductionmentioning

confidence: 99%

The osteopontin – CD44 pathway is superfluous for the development of autoimmune myocarditis

et al. 2006

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Osteopontin (OPN) and CD44 have been implicated in the development of autoimmune diseases, including arthritis and multiple sclerosis, as well as chronic inflammatory diseases, such as atherosclerosis and colitis. To investigate their roles in autoimmune myocarditis induced by immunization with heart alpha‐myosin (MyHC‐α), a mouse model of human cardiomyopathy, we analyzed mice lacking OPN or CD44v6/v7, a CD44 isoform that binds OPN. Both, OPN–/– and CD44v6/v7–/– mice developed myocarditis with the same prevalence and severity as BALB/c wild‐type controls. Furthermore, treatment of BALB/c mice with a pan‐neutralizing anti‐CD44 antibody did not affect the disease outcome. Consistently, expansion of MyHC‐α‐specific autoimmune CD4+ T cells and MyHC‐α autoantibody responses from either CD44v6/v7–/– mice or OPN–/– mice was indistinguishable from their wild‐type controls. Thus, OPN and CD44v6/v7 are merely spectators rather than protagonists in autoimmune myocarditis.

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“…Mice are advantageous models because they share similar genetics to humans, they are cost-effective in handling and breeding, many transgenic strains are available and they are responsive to cardiotropic viruses (Cunningham 2001;Fairweather et al 2001;Esfandiarei et al 2008). Coxsackievirus B3 has been detected in 30-50% of dilated cardiomyopathy patients, providing support for a coxsackievirus B3-induced myocarditis mouse model (Escher et al 2011).…”

Section: In Vivo Experimental Systemsmentioning

confidence: 99%

“…In fact, following IP injection, three distinct immunovirological phases of disease have been observed. In mice, coxsackievirus B3 can induce two forms of inflammatory heart disease, acute only or acute and chronic (biphasic) autoimmune disease (Horwitz et al 2000;Cunningham 2001;Fairweather et al 2001). Interestingly, coxsackievirus B3 replication is mainly observed in the pancreas and to a lesser extent in the heart.…”

Section: In Vivo Experimental Systemsmentioning

confidence: 99%