Spontaneous autoimmune myocarditis and cardiomyopathy in HLA-DQ8.NODAbo transgenic mice

Veena Taneja, Chella S. David

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Most individuals have viral infections at some point in their life, however, only few develop autoreactivity to cardiac myosin following infection suggesting a genetic predisposition. Population studies have shown that among all the genetic factors linked with autoimmune disease development, MHC class II genes are the most significant genetic factors. Experimental autoimmune myocarditis resembling human Dilated cardiomyopathy can be induced in susceptible mice by infection with coxsackie virus as well as immunization with purified foreign and murine cardiac specific a-myosin. We generated transgenic mice lacking endogenous class II molecules, HLA-DR3.Abo and HLA-DQ8.Abo transgenic mice in NOD and HLA-DQ8.Abo in B10 background, to study the role of MHC in spontaneous autoimmunity. The HLA molecules in these mice are expressed on cell surface and can positively select CD4+ T cells expressing various Vb T cell receptors. NOD.DQ8 female mice spontaneously developed myocarditis and dilated cardiomyopathy. Histopathology of heart revealed mononuclear infiltrate consisting of CD4 and Mac-1+ cells and myocyte necrosis. NOD.DQ8 mice showed cellular and humoral autoreactive response to self cardiac myosin.. Depletion of CD8 and CD4 + cells suggested that CD8 T cells may act as regulatory cells while CD4 cells are required as effector cells. NOD.DR3 and B10.DQ8 mice did not develop any cardiac pathology suggesting DQ8 is required for predisposition to the spontaneous autoreactivity while NOD background influences onset and progression of disease. Thus these mice provide powerful tools to understand the role of HLA class II molecules in predisposition and onset of human diseases and to develop immunotherapy.

Original languageEnglish (US)
Pages (from-to)260-269
Number of pages10
JournalJournal of Autoimmunity
Volume33
Issue number3-4
DOIs
StatePublished - Nov 2009

Keywords

  • Cardiac myosin
  • Dilated cardiomyopathy
  • HLA transgenic mice
  • MHC polymorphism
  • Myocarditis
  • Regulatory cells
  • Spontaneous autoreactivity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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