Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 197, Issue 3, Pages 323-331Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021788
Keywords
dendritic cells; interleukin 1; interleukin 1 receptor type 1; autoimmunity; myocarditis
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Dilated cardiomyopathy, resulting from myocarditis, is the most common cause of heart failure in young patients. We here show that interleukin (IL)-1 receptor type 1-deficient mice are protected from development of autoimmune myocarditis after immunization with alpha-myosin-peptide(614-629). CD4(+)T cells from immunized IL-1R1(-/-) mice proliferated poorly and failed to transfer disease after injection into naive severe combined immunodeficiency (SCID) mice. In vitro stimulation experiments suggested that the function of IL-1R1(-/-)CD4(+)T cells was not intrinsically defect, but their activation by dendritic cells was impaired in IL-1R1- mice. Accordingly, production of tumor necrosis factor (TNF)-alpha, IL-1, IL-6, and IL-12p70 was reduced in dendritic cells lacking the IL-1 receptor type 1. In fact, injection of immature, antigen-loaded IL-1R1(+/+) but not IL-1R1(-/-) dendritic cells into IL-1R1(-/-) mice fully restored disease susceptibility by rendering IL-1R1(-/-) CD4(+)T cells pathogenic. Thus, IL-1R1 triggering is required for efficient activation of dendritic cells, which is in turn a prerequisite for induction of autoreactive CD4(+) T cells and autoimmunity.
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