Neutrophils sustain pathogenic CD8+ T cell responses in the heart

Am J Pathol. 2003 Dec;163(6):2413-20. doi: 10.1016/S0002-9440(10)63596-1.


This study explores the influence of innate immunity on CD8(+) T-cell responses against heart tissue. Adoptive transfer of ovalbumin-specific CD8(+) effector T cells into CMy-mOva mice, which express ovalbumin in cardiac myocytes, results in a lethal acute myocarditis. The inflammatory infiltrate in the heart includes neutrophils as well as T cells. We used anti-Ly6G antibody to transiently deplete neutrophils at the time of onset of disease. By day 7 after receiving 5 x 10(5) CD8(+) effector T cells, 100% of control Ig-treated CMy-mOva mice had died, while 85% of anti-Ly6G-treated mice survived indefinitely. CD8(+) T-cell infiltration and tissue damage were present in both groups, but the disease was limited in the anti-Ly6G-treated mice, with a rapid disappearance of the adoptively transferred CD8(+) T cells within 11 days. Recovery occurred even though blood neutrophil counts began to rise 48 hours after the last anti-Ly6G treatment. Recovery was associated with a chronic CD4(+) cell infiltrate, and a rapid decline in expression of IFN-gamma and IP-10 mRNA in the myocardium. Neutrophil depletion did not effect survival of CMy-mOva mice that received 3 x 10(6) CD8(+) T cells. These data show that granulocytic inflammation sustains CD8(+) T-cell-mediated heart disease, which has important implications for the pathogenesis and treatment of acute myocarditis and allograft rejection.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Antigens, Ly / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cells, Cultured
  • Egg Proteins / immunology
  • Heart / physiopathology
  • Mice
  • Mice, Transgenic
  • Myocarditis / immunology*
  • Myocarditis / pathology
  • Myocarditis / physiopathology
  • Myocardium / pathology
  • Neutrophils / immunology*
  • Neutrophils / pathology
  • Ovalbumin / immunology
  • Peptide Fragments
  • Recovery of Function
  • Severity of Illness Index
  • Time Factors


  • Antibodies
  • Antigens, Ly
  • Egg Proteins
  • Ly6G antigen, mouse
  • OVA-8
  • Peptide Fragments
  • Ovalbumin