Natural killer cells suppress autoimmune myocarditis in mice (48.23)

Abstract

Abstract Autoimmune myocarditis is induced by the adoptive immune response; however, there is evidence that the innate immune system plays a major role in modulating disease. Natural killer (NK) cells can function in early innate responses, as well affecting the later adaptive immune response. Depletion of NK cells has been shown to exacerbate the development of virus-induced myocarditis. We hypothesized that NK cells also modulate the virus-free model of myosin-induced experimental autoimmune myocarditis (EAM). To study the action of NK cells, we immunized BALB/c mice on days 0 and 7 with myocarditogenic peptide MyHC (614-629) in complete Freund adjuvant. The mice were treated with PBS, rabbit IgG or anti-asialo GM1 antibody every day for 6 days prior to the first immunization and every 2 days following day 0 until day 21. We found that depleting NK cells significantly increased the severity of disease, and serum antibodies specific to the myocarditogenic peptide. Splenic CD4+ T cells were significantly more activated in NK depleted mice compared to controls. Cytokine analysis of heart homogenates revealed a significant increase in eotaxin and IL-5 in the hearts of mice that were depleted of NK cells. Our data suggest that NK cells suppress the adoptive immune response and modulate eosinophil migration and T cell activation during EAM in mice.