TY - JOUR
T1 - Type I IFN-beta gene therapy suppresses cardiac CD8+ T-cell infiltration during autoimmune myocarditis
AU - Bartlett, Emmalene J
AU - Lenzo, Jason C
AU - Sivamoorthy, Soruba
AU - Mansfield, Josephine P
AU - Cull, Vanessa S
AU - James, Cassandra M
PY - 2004/4
Y1 - 2004/4
N2 - Gene therapy using DNA encoding type I IFN subtypes IFNA6, IFNA9 and IFNB suppresses murine cytomegalovirus (MCMV)-myocarditis, a predominantly cell-mediated disease in BALB/c mice. CD8(+) T cells are the principal cell type within the inflamed myocardium. As such, we investigated the effects of IFN subtype treatment on this T-cell subset and other cell types in the cardiac infiltrate. In the acute phase of disease, IFNA6 and IFNA9 treatments significantly reduced the number of CD8(+) T cells within the foci of cellular infiltration in the heart. During the chronic phase, which is primarily autoimmune in nature, IFNB treatment significantly reduced CD8(+) T cells. B-cell and neutrophil numbers in the cardiac infiltrate were also reduced following IFNB immunotherapy. Although early inflammatory responses are important for resolution of virus infection, high numbers of lymphocytes persisting in the myocardium may lead to exacerbation of disease. Our data suggests that type I IFN DNA therapy regulates cardiac cellular infiltration. Thus, treatment with IFN-beta administered prophylactically to high-risk patients in acquiring CMV infection may reduce the development of chronic autoimmune myocarditis.
AB - Gene therapy using DNA encoding type I IFN subtypes IFNA6, IFNA9 and IFNB suppresses murine cytomegalovirus (MCMV)-myocarditis, a predominantly cell-mediated disease in BALB/c mice. CD8(+) T cells are the principal cell type within the inflamed myocardium. As such, we investigated the effects of IFN subtype treatment on this T-cell subset and other cell types in the cardiac infiltrate. In the acute phase of disease, IFNA6 and IFNA9 treatments significantly reduced the number of CD8(+) T cells within the foci of cellular infiltration in the heart. During the chronic phase, which is primarily autoimmune in nature, IFNB treatment significantly reduced CD8(+) T cells. B-cell and neutrophil numbers in the cardiac infiltrate were also reduced following IFNB immunotherapy. Although early inflammatory responses are important for resolution of virus infection, high numbers of lymphocytes persisting in the myocardium may lead to exacerbation of disease. Our data suggests that type I IFN DNA therapy regulates cardiac cellular infiltration. Thus, treatment with IFN-beta administered prophylactically to high-risk patients in acquiring CMV infection may reduce the development of chronic autoimmune myocarditis.
KW - Animals
KW - Autoimmune Diseases/immunology
KW - DNA/metabolism
KW - Dendritic Cells/immunology
KW - Genetic Therapy
KW - Interferon-alpha/genetics
KW - Interferon-beta/genetics
KW - Leukocytes/immunology
KW - Male
KW - Mice
KW - Myocarditis/immunology
U2 - 10.1046/j.0818-9641.2004.01234.x
DO - 10.1046/j.0818-9641.2004.01234.x
M3 - Article
C2 - 15061762
SN - 0818-9641
VL - 82
SP - 119
EP - 126
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
IS - 2
ER -