A locus on chromosome 1 promotes susceptibility of experimental autoimmune myocarditis and lymphocyte cell death

Davinna L. Ligons, Mehmet L. Guler, Haiyan S. Li, Noel R. Rose

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalClinical Immunology
Volume130
Issue number1
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Apoptosis
  • Autoimmune
  • Caspase
  • Chromosome
  • Gene
  • Locus
  • Myocarditis
  • Regulation
  • Rodent
  • Susceptibility

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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