Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts

J Clin Invest. 1997 Aug 1;100(3):550-7. doi: 10.1172/JCI119564.

Abstract

We have hypothesized that T cell cytokines participate in the pathogenesis of graft arterial disease (GAD). This study tested the consequences of IFN-gamma deficiency on arterial and parenchymal pathology in murine cardiac allografts. Hearts from C-H-2(bm12)KhEg (bm12, H-2(bm12)) were transplanted into C57/B6 (B6, H-2(b)), wild-type, or B6 IFN-gamma-deficient (GKO) recipients after immunosuppression by treatment with anti-CD4 and anti-CD8 mAbs. In wild-type recipients, myocardial rejection peaked at 4 wk, (grade 2. 1+/-0.3 out of 4, mean+/-SEM, n = 9), and by 8-12 wk evolved coronary arteriopathy. At 12 wk, the GAD score was 1.4+/-0.3, and the parenchymal rejection grade was 1.2+/-0.3 (n = 8). In GKO recipients of bm12 allografts, myocardial rejection persisted at 12 wk (grade 2.5+/-0.3, n = 6), but no GAD developed (score: 0.0+/-0.0, n = 6, P < 0.01 vs. wild-type). Mice treated with anti-IFN-gamma mAbs showed similar results. Isografts generally showed no arterial changes. In wild-type recipients, arterial and parenchymal cells showed increased MHC class II molecules, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 compared to normal or isografted hearts. The allografts in GKO recipients showed attenuated expression of these molecules (n = 6). Thus, development of GAD, but not parenchymal rejection, requires IFN-gamma. Reduced expression of MHC antigens and leukocyte adhesion molecules may contribute to the lack of coronary arteriopathy in hearts allografted into GKO mice.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Coronary Artery Disease / prevention & control*
  • Graft Rejection / prevention & control*
  • Heart Transplantation*
  • Interferon-gamma / deficiency*
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Transplantation, Homologous

Substances

  • Antibodies, Monoclonal
  • Interferon-gamma