Interferon‐γ plays a nonredundant role in mediating T‐cell‐ dependent outward vascular remodeling of allogeneic human coronary arteries

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Abstract
SPECIFIC AIMSWe investigated the cellular and molecular mechanisms of T cell-mediated outward vascular remodeling using a human/mouse chimeric model.PRINCIPAL FINDINGS1. In vivo model of allogeneic human coronary artery rejectionHuman epicardial coronary arteries (6–8 mm long and 0.5–1 mm in diameter) were bisected and microsurgically interposed into the aortae of paired severe combined immunodeficient (SCID)/beige mice. One animal received an adoptive transfer of 3 × 108 allogeneic (to the artery) human peripheral blood mononuclear cells (PBMCs) i.p. 1 wk postoperatively and the other recipient was untreated. The adjacent human arterial segments were used as matched investigational and control grafts to account for size and morphological differences between individual donor vessels. T cells were detected only in the circulation of animals that received PBMCs (9.5±1.5% human CD3+ cells/mouse CD45+ cells after 2 wk). Paired animals (n=64) were killed at 2, 4, or 6 wk after immune reconstitution and grafts ...
Funding Information
  • National Institutes of Health (PO1 HL70295‐01)