A Locus on Chromosome 1 Promotes Susceptibility of Experimental Autoimmune Myocarditis and Lymphocyte Cell Death1

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2008-10, Vol.130 (1), p.74-82
• Main Authors: Ligons, Davinna L., Guler, Mehmet L., Li, Haiyan S., Rose, Noel R.
• Format: Article
• Language: English
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2008.06.015

We previously identified by linkage analysis a region on chromosome 1 ( Eam1 ) that confers susceptibility to experimental autoimmune myocarditis (EAM). To evaluate the role of Eam1 , we created a congenic mouse strain, carrying the susceptible Eam1 locus of A.SW on the resistant B10.S background (B10.A- Eam1 congenic) and analyzed three outcomes: 1) the incidence and severity of EAM, 2) the susceptibility of lymph node cells (LNCs) to Cy-enhanced cell death, and 3) susceptibility of lymphoctyes to antigen-induced cell death. Incidence of myocarditis in B10.A- Eam1 congenic mice was comparable to A.SW mice, confirming that Eam1 plays an important role in disease development. Caspase 3, 8 and 9 activation in LNCs following Cy treatment and in CD4 + T cells after immunization with myosin/CFA was significantly lower in A.SW than B10.S mice whereas B10.A- Eam1 congenic mice exhibited an intermediate phenotype. Our results show that Eam1 reduces lymphocyte apoptosis and increases susceptibility to EAM.