IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis

J Clin Invest. 2003 Mar;111(5):671-80. doi: 10.1172/JCI16867.


Cardiac antigen-specific CD8(+) T cells are involved in the autoimmune component of human myocarditis. Here, we studied the differentiation and migration of pathogenic CD8(+) T cell effector cells in a new mouse model of autoimmune myocarditis. A transgenic mouse line was derived that expresses cardiac myocyte restricted membrane-bound ovalbumin (CMy-mOva). The endogenous adaptive immune system of CMy-mOva mice displays tolerance to ovalbumin. Adoptive transfer of naive CD8(+) T cells from the ovalbumin-specific T cell receptor-transgenic (TCR-transgenic) OT-I strain induces myocarditis in CMy-mOva mice only after subsequent inoculation with ovalbumin-expressing vesicular stomatitis virus (VSV-Ova). OT-I effector T cells derived in vitro in the presence or absence of IL-12 were adoptively transferred into CMy-mOva mice, and the consequences were compared. Although IL-12 was not required for the generation of cytolytic and IFN-gamma-producing effector T cells, only effectors primed in the presence of IL-12 infiltrated CMy-mOva hearts in significant numbers, causing lethal myocarditis. Furthermore, analysis of OT-I effectors collected from a mediastinal draining lymph node indicated that only effectors primed in vitro in the presence of IL-12 proliferated in vivo. These data demonstrate the importance of IL-12 in the differentiation of pathogenic CD8(+) T cells that can cause myocarditis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / physiology*
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / pharmacology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Myocarditis / etiology*
  • Myocarditis / immunology
  • Organ Specificity
  • Ovalbumin / immunology


  • Interleukin-12
  • Interferon-gamma
  • Ovalbumin